Palillo died of a heart attack early Tuesday in Palm Beach Gardens, Florida, his agent told CNN.
Palillo played the class clown, who yelped, "Oooh, oooh," as his hand shot skyward when a teacher posed a question, on the ABC sitcom from 1975 to 1979. While "Welcome Back, Kotter" was a ratings success and the show helped launch the film career of co-star John Travolta, Palillo struggled to expand beyond his role as Horshack.
He said he felt exiled throughout the 1980s, unable to find parts, sinking into depression, and rarely venturing from his apartment. When offers did come, he felt typecast as Horshack.
"While I loved him, I really loved him, I didn't want to do him forever," he told the Birmingham News in 1994.
Palillo made his big screen debut in the 1979 movie "Skatetown, U.S.A." and later appeared in films such as "Jason Lives: Friday the 13th Part VI" in 1986 and "Hellgate" in 1990. He also had small roles on TV shows such as "The Love Boat" and ''Cagney and Lacey" and played Gary Warren on the ABC soap opera "One Life to Live."
Palillo was born April 2, 1949, in Cheshire, Conn. His father died of lung cancer when he was 10 and he developed a stutter. His mother thought getting him involved in a local theater might help. He fell in love with the stage. He attended the University of Connecticut and earned parts in Shakespearean productions before his big break.
When he auditioned for "Kotter," he thought he'd be passed over for others who had more of a tough-guy New York look. His dying father's voice inspired his character's wheezing laugh, he told the News.
The Associated Press contributed to this report.