Motivated by a need for a place where he could hang out with friends, listen to music of their liking and perform when they wanted, Johnny and fellow musician Chuck E. Weiss, opened a night club in Hollywood, California. Under the management of Johnny's childhood friend Sal Jenko, The Viper Room featured live music, and soon became a popular hangout for Hollywood's young actors.
The Viper Room's intimate setting appealed to many popular musicians. Tom Petty and the Heartbreakers played opening night on August 14, 1993. Johnny and his band, P, took the stage sometimes, joined occasionally by Flea from the Red Hot Chili Peppers and Steve Jones of the Sex Pistols. Bruce Springstein once held an impromptu concert at The Viper Room. In December 1993, Johnny Cash took the stage and was introduced by Johnny with the following: "Ladies and gentlemen, I can't believe I get to say this: Johnny Cash!" Two songs Cash performed that night were recorded and included on his album American Recordings.
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Only months after its opening, The Viper Room gained tragic notoriety. Early Halloween morning in 1993, River Phoenix, present to perform with Flea, collapsed outside and died of a drug overdose. Johnny was deeply affected by River's death and the rumors that surrounded it. He closed the club and posted a sign near the entrance that read, "With much respect and love to River and his family, The Viper Room has been temporarily closed. Our heartfelt condolences to all his family, friends and loved ones. He will be missed." River's fans were allowed to leave memorials at the site. Flowers, candles, and other mementos were placed outside the entrance to the club, and fans covered the club doors with graffiti. The Viper Room reopened two weeks later. Until 2004 when Johnny passed on his shares in the club, The Viper Room was closed every Halloween.