From the Medical Heritage Library, new information about Knighton's early medical career – definitely before 1813, when he received his baronetcy, and probably between 1798 to 1803, successful but difficult years when he was in private practice in Plymouth.  

In 1815 the Berks and Bucks Vaccine Institution published a paper to promote vaccination with cowpox as a safer alternative to inoculation with smallpox. A footnote said that some years earlier the then Dr Knighton took matter from the arm of a girl who had developed cowpox following vaccination, and inserted it into one of his patients where it 'produced the disease in a satisfactory manner'.  

This account is entirely plausible. The girl was the younger daughter of a Plymouth physician, Thomas Stewart, who vaccinated her in early 1801 when Knighton was still practising in Plymouth. The young Dr Knighton did not have happy memories of these years; his comment on a bruising incident with unnamed local colleagues was, 'Everything that is wrong punishes itself'. 

In 1803 Knighton left Plymouth for London, and a year later Stewart wrote up the results of vaccination on his own children. If he had ever collaborated with the young doctor who had since left the area, he didn’t bother to mention him.

Knighton, a connoisseur of art and a patron of artists, liked and admired Lawrence. When Knighton became Keeper of the Privy Purse to George IV in the autumn of 1822, it was Lawrence who painted his portrait. Rumour had it that Knighton's son later studied under Lawrence, and when Lawrence died his works in progress included a portrait of Knighton's wife.

Lawrence completed his portrait of Knighton in time for the  Royal Academy exhibition the following summer, but he was not always so efficient. And when unfinished works were commissions from George IV it was Knighton's job to chivvy Lawrence along. In 1824 Knighton tried to coax him into completing a portrait that George IV had commissioned at least three years earlier.  The sitter was Lady Elizabeth Conyngham, the daughter of George IV's last lady companion, Marchioness Conyngham.  

In October Knighton wrote Lawrence a good-humoured letter to convey the King's wish that Lawrence bring Lady Elizabeth's portrait to Windsor and complete it there. Nevertheless this was a royal command and Knighton cautioned Lawrence, 'You must have the goodness, not to fail in this particular!' Knighton's tact failed. A month later the portrait remained unfinished, and Lawrence received a formal note informing him that Sir William Knighton was honoured with the King's command that Sir Thomas Lawrence finish Lady Elizabeth's portrait without delay and send it to Carlton House.  

This curt, third-person tone was not typical of Knighton's dealings with Lawrence.  Whenever possible - and certainly in private correspondence - Knighton treated him with affectionate esteem. He confided to Lawrence that every time he entered Lawrence's rooms he was overcome with a desire to own everything in them. When Lawrence suffered a severe cold Knighton sent him two pills to be taken on going to bed and recommended that he have a basted chicken for dinner. 

After Lawrence's death in January 1830 Knighton wrote, 'There seems to be a void in the congregated mass of society:  you turn to the right and to the left – you have no substitute for him.'

Portrait of Lady Elizabeth Conyngham by Thomas Lawrence, 1821-1824
From Wikimedia Commons

Portrait of Mrs Jens Wolff  by Thomas Lawrence, 1803-1815 
From Wikimedia Commons

Isabella Wolff was Lawrence's close friend and perhaps his mistress, but my interest in the portrait is its background: was it painted at Sherwood Lodge, the Battersea house that Knighton bought from Isabella's husband around 1813-1814?  An 1820 catalogue description of papered walls, fluted pillars and 'Gothic style' rules out most rooms, but the billiard room, said to be decorated with bas reliefs, is a possibility.

Another Lawrence portrait of Isabella Wolff, showing a Regency hair-do in detail.
A website dedicated to Lawrence. 
The archive of Archibald Keightley, Lawrence's executor.  I should have seen this to find out more about the unfinished portrait of Lady Knighton
Lawrence's portrait of Knighton, described by one visitor to the Royal Academy exhibition as 'the very perfection of portrait painting'.

William Knighton started his London practice in 1806; by 1812 he was said to have connections with almost every family of distinction. During the next ten years his patients included Leigh Hunt and his family; Richard Wellesley, 1st Marquess Wellesley, introduced by Wellesley's mistress; the family of John Wilson Croker; Harriet Canning,  George Canning's young daughter;  Lady Charlotte Grimston, Countess of Verulam, sister to Lord Liverpool;  Henry Gage, 3rd Viscount Gage; the  Countess of Warwick (portrait); Byron; and novelist Catherine Stepney. After Princess Charlotte's death he spoke to several of her close friends, including mother and daughter Lady Anne Smith and the Marchioness of Worcester, to assure them that Croft's conduct had been correct. So when Knighton became a full-time courtier in 1822 he was already a household name in the best households. 

On entering the King's service Knighton gave up his medical practice, but he did not give up medicine. Artist and fellow Devonian Samuel Prout, incapacitated by headaches, overcame his embarrassment at approaching his former physician and asked for a prescription that Knighton had successfully prescribed for him many years earlier. Harriett Arbuthnot was also grateful for a prescription from Knighton, despite calling him 'a great rogue and a blackguard'. On retirement to the country after George IV's death Knighton gave medical advice to anyone who asked. 

Knighton's treatments were conservative. He favoured bleeding, recommending his wife to apply not more than half a dozen leeches to her temples if she felt headachy or bilious. He disapproved of cold-water bathing as a remedy. He enjoyed his food, but preached and practised moderation. When he travelled to Spain with Richard Wellesley he took a portable bed to avoid lice, and warned his party of the dangers of bad water. On occasion, perhaps believing that hope was his only remaining remedy, he gave reassurance that he must have known was ill founded. But it was also said that he was able to gain control over his patients' minds, much to their benefit.

Knighton, Croft, and Princess Charlotte: After publication I discovered new material. It's discussed towards the end of the comments here.

As Knighton's London practice increased he wrote that he was making valuable connections who handed him over from one circle of people to another. Had he wished to give an example, the poets of Regency London would have made his point. 

In 1812 Coleridge, bedridden and opium addicted, consulted Robert Gooch, a physician with whom Knighton had studied medicine at Edinburgh, and whom Knighton encouraged to practise in London.   

In March 1813 Leigh Hunt, a patient of Knighton, was imprisoned for libelling the Prince Regent. Knighton was by then physician-in-ordinary to the Regent and, believing that his visits to Hunt's cell would be exploited by the Regent's critics, he arranged for Gooch to attend Hunt instead.  Knighton treated Hunt's family without charge, and lent him money which was probably repaid through the intervention of Shelley. 

Coleridge and Hunt were connections of Byron, a patient whom Knighton advised against marriage, and to whom he introduced the phrenologist Johann Spurzheim.  Coleridge was also colleague and brother-in-law to Robert Southey. Robert's brother Henry studied at Edinburgh with Knighton and Gooch, and on Knighton's advice he too moved to London to practise. In 1817, when Robert was on the Continent, he reported to Knighton on the ill-considered conduct of Princess Caroline while abroad. Knighton's transition to full-time courtier had begun, but it would be another five years before he gave up his practice. So when one of Hunt's children became dangerously ill a week before George IV's coronation in July 1821, Knighton made a midnight call to attend her.

***

Secondary sources disagree about whether it was Knighton or Sir Henry Halford who