The Sixth Doctor's regeneration was initially unstable, and he nearly strangled Peri before he came to his senses. Realising what he had nearly done, he initially considered going into a hermitlike existence on the planet Titan 3, only to be caught up in events on the planet Jocanda, after which he resumed his travels (The Twin Dilemma). He encountered many old foes including the Master, Daleks, Cybermen and Sontarans, and even shared an adventure with his own second incarnation. He also faced a renegade female Time Lord scientist, the Rani, who was conducting experiments on humans using the Luddite Riots as a cover.
Later, the Doctor and Peri landed on the devastated planet Ravolox, which they discovered was actually Earth, moved across space with devastating consequences. Before they could discover the reason for this disaster, the TARDIS landed on Thoros Beta. What actually happened here is still unclear, but initial accounts suggest that Peri was killed after being cruelly used as a test subject in brain transplant experiments and the Doctor was pulled out of time to a Time Lord space station where he was put on trial for the second time by his own race, the Time Lords. In reality the trial was a cover-up organised by the High Council. A race from Andromeda had stolen Time Lord secrets and hidden on Earth, so in order to protect themselves the Time Lords had moved Earth through space, burning the surface in a massive fireball and leaving it as Ravolox. The prosecutor at that trial, the Valeyard, turned out to be a possible future, an evil incarnation of the Doctor himself who was out to steal his remaining lives. He had also edited the Matrix recordings of the Doctor's travels; in reality Peri had survived events on Thoros Beta. The events of the trial tangled the Doctor's timeline slightly, as he left in the company of Mel, whom he technically had not yet met. (Originally this was the then-producer's idea that in the following season this would be explained).
Events following the trial are not covered in the television series, but are covered in various spin-off media, though their canonicity is unclear. The Virgin Missing Adventuresnovel Time of Your Life states that the Doctor went into a self-imposed exile to avoid becoming the Valeyard. He was lured back into travelling, ironically by the Time Lords, and recruited Grant Markham as a companion. Although now travelling again, he still attempted to avoid meeting Mel and recruited other companions such as history lecturerEvelyn Smythe and Charley Pollard. He eventually does encounter Mel by accident during the events of the BBC Books novel Business Unusual and accepts his fate once she stows away in the TARDIS.
When the TARDIS was attacked by his old enemy the Rani, the Sixth Doctor was somehow injured and regenerated into the Seventh Doctor; the exact cause of the regeneration, however, has never been revealed on-screen. When writers Pip and Jane Baker's novel of the story tried to explain the regeneration many were not happy with the outcome. There have subsequently been various explanations for the regeneration. The Virgin New Adventures series suggests that the Seventh Doctor somehow killed the Sixth, because he could not become the masterplanner and manipulator that his next incarnation became, due to his fear of becoming the Valeyard. The BBC Booksnovel Spiral Scratch offers an alternative explanation that the Sixth Doctor died as a result of his chronal energy being drained in a confrontation with a powerful pan-dimensional entity before being snared by the Rani's beam.
The Sixth Doctor was an unpredictable and somewhat petulant egoist, whose garish, multicoloured attire reflected his volatile personality. He was both portentous and eloquent, even for the Doctor - of whom he saw himself as the finest incarnation yet – and his unpredictability was made even wilder by his mood swings, manic behaviour, bombastic outbursts and glib, unflappable wit. His personality also displayed occasionally fatalistic overtones.
The Sixth Doctor was almost supremely confident in his abilities and did not suffer fools gladly; he sometimes seemed to endure Peri's presence far more than he actually appreciated it, and his superiority complex applied to almost everyone he encountered. His intellect could support his ego; for instance, the Sixth Doctor was the only one who was able to repair and operate the Chameleon Circuit within the TARDIS, allowing it to change shape to suit its surroundings rather than looking constantly like a police box (although the appropriateness of the TARDIS's appearance to its environment was more-or-less nil) in Attack of the Cybermen. However, not only did his melodramatic arrogance and caustic wit eventually subside, it actually hid the fact that this incarnation retained the Doctor's strong moral sense and empathy, as seen in Revelation of the Daleks, in which he showed great compassion for a dying mutant; and The Trial of a Time Lord, where he displayed outrage at his own people for their part in a plot and cover-up which resulted in the death of most of the Earth's population. Underneath his blustering exterior, he was more determined than ever in his universal battles against evil, possessed of a tenacity and a thirst to do what was right that was far more visible than ever before. Despite his often unstable demeanour, he was always ready to act when necessary, and very little – even his companions – could hope to stand in his way.
His condescension towards the universe around him also extended to his companions, especially Peri. While his use of violence against his foes and his abrasive relationship with Peri were both often criticised by fans, the violence was largely in self-defence, and his relationship with Peri had mellowed significantly when the programme returned from hiatus for Season 23's The Trial of a Time Lord.
He was well known for his love of cats, and always wore one of a number of cat-shaped pins or brooches on the lapel of his patchwork coat, itself said to be the height of fashion on a distant planet.
The events surrounding the production of Doctor Who in the mid-1980s caused the Sixth Doctor's tenure to be cut short, and for a long time Colin Baker bore the brunt of the blame as the "unlikeable" Doctor.
During the Sixth Doctor's tenure in the Big Finish Productions audio plays, voiced by Baker, he appeared to be a somewhat calmer, wittier and altogether happier character (attributed in-story to the influence of companion Evelyn Smythe). In a 2001 poll in Doctor Who Magazine, Baker was voted the "greatest Doctor" of the audio plays. Baker has said that he was not given enough time in the 1980s to 'unpeel the layers' of his character.