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He had expanded into producing and arranging by the 1960s. He also began concentrating on his keyboard skills after a gun accident forced him to give up the guitar. After brushes with the law and drugs he left New Orleans to get away from the troublesome environment. He ended up in Los Angeles where he found session work. It was at this time that Rebennack renamed himself Dr. John. The Night Tripper, as he called himself, released his first album, Gris-Gris. Rumor has it the album was hastily cut together during left over studio time after a Sonny & Cher session. The finished album never revealed its rushed production. The mix of R&B and voodoo sounds combined with a psychedelic tinge had critics and fans enthralled. An underground following quickly formed and followed him to his eccentric stage shows around the LA area. He became the talk of the town in his Mardi Gras costume performing ceremonial events on stage.

Dr. John's next few albums received mixed reviews, but his fans stuck by. Some, like The Sun, Moon & Herbs, were appreciated more than others. The album featured Eric Clapton and Mick Jagger, a surprising addition to Dr. John's line-up. The 1972 release of Gumbo, produced by Jerry Wexler, was a great success. Fans loved Dr. John's trip back to traditional New Orleans R&B, reliving his days with greats like Professor Longhair. His biggest hit came in 1973. "In the Right Place" was produced by Allen Toussaint and was backed by the Meters. The same year he also recorded the Triumvirate album with Mike Bloomfield and John Hammond Jr.

During the next ten years Dr. John did not come up with any new hits, but his traditional pieces always got the crowds to their feet. Throughout the 80s he toured with a more classically inclined show, falling back on his roots in New Orleans R&B. He released solo piano albums during that time, as well as sessions with Chris Barber and Jimmy Witherspoon. The albums did not sell well. He soon turned to a more lucrative business'”singing as the voice talent for commercial jingles. He continued touring through the 80s and 90s without producing commercial success with his recordings. He published an autobiography in 1994, titled Under a Hoodoo Moon. After a few years away from the industry he resurfaced with the release of Anutha Zone, which featured collaborations with performers like Spiritualized, Paul Weller, Supergrass, and Ocean Colour Scene. Dr. John has continued touring with his unique voodoo music and eclectic stage presence to packed houses across the country.