Barrett became increasingly erratic, partly as a consequence of his reported heavy use of psychedelic drugs such as LSD. There is also speculation that he suffered from schizophrenia. Once described as joyful, friendly, and extroverted, he became increasingly depressed and socially withdrawn, and experienced hallucinations, disorganized speech, memory lapses, intense mood swings, and periods of catatonia. Although the changes began gradually, he went missing for a long weekend and, according to several friends, including Wright, came back "a completely different person."
One of the striking features of his change was the development of a blank, dead-eyed stare. He did not recognise old friends, and often did not know where he was; while on a tour of Los Angeles, Barrett is said to have exclaimed, "Gee, it sure is nice to be in Las Vegas!" Many reports described him on stage, strumming one chord through the entire concert, or not playing at all. At a show at The Fillmore in San Francisco, during a performance of "Interstellar Overdrive", Barrett slowly detuned his guitar. The audience seemed to enjoy such antics, unaware of the rest of the band's consternation.
Interviewed on Pat Boone's show during this tour, Barrett's reply to Boone's questions was a "blank and totally mute stare"; according to Mason, "Syd wasn't into moving his lips that day." Barrett exhibited similar behaviour during the band's first appearance on Dick Clark's popular TV show American Bandstand. Although surviving footage of this appearance shows Barrett miming his parts of the song competently, during a group interview afterwards, when asked two questions by Clark, Barrett's answers were terse, almost to the point of rudeness (though, Clark noted, they had flown non-stop from London to Los Angeles). During this time, Barrett would often forget to bring his guitar to sessions, damage equipment and occasionally was unable to hold his pick. Before a performance in late 1967, Barrett reportedly crushed Mandrax tranquilliser tablets and a tube of Brylcreem into his hair, which subsequently melted down his face under the heat of the stage lighting, making him look like "a guttered candle". Mason disputed the Mandrax portion of this story, stating that "Syd would never waste good mandies."
During their UK tour with Jimi Hendrix in November 1967, guitarist David O'List from The Nice substituted for Barrett on several occasions when he was unable to perform or failed to appear. Sometime around Christmas, Barrett's schoolfriend David Gilmour was asked to join the band as a second guitarist to cover for Barrett, with the idea of retaining a five-member line-up of the band. For a handful of shows, Gilmour played and sang while Barrett wandered around on stage, occasionally joining the playing. The other band members soon grew tired of Barrett's antics and, on 26 January 1968, when Waters was driving on the way to a show at Southampton University, the band elected not to pick Barrett up: one person in the car said, "Shall we pick Syd up?" and another said, "Let's not bother." As Barrett had, up until then, written the bulk of the band's material, the initial plan was to keep him in the group as a non-touring member—as the Beach Boys had done with Brian Wilson—but this proved impractical. Gilmour subsequently became a full-time member of the band.