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To examine the use of alcohol and illicit drugs among HIV-positive gay and bisexual men and to determine substance-use-related predictors of unprotected sex with casual partners who were HIV negative, HIV positive, or whose serostatus was unknown.Cross-sectional assessment of baseline data from a behavioral intervention.From 1999 to 2001, we recruited 1168 HIV-positive gay and bisexual men in New York City and San Francisco and determined the prevalence of drinking and drug use, as well as the use of substances with sex. We then examined associations between substance use variables and risky sexual behaviors with casual partners by partner serostatus.Substance use was common, and the use of ‘party drugs’ [e.g. methamphetamine, nitrate inhalants (poppers), ketamine, and gamma hydroxybutyrate] was most often associated with sexual risk in multivariate models. Substance use before or during sex was not associated with risk with HIV-negative partners, but was associated with risk with HIV-positive and unknown-serostatus partners.Substance use before or during sex was not associated with risk with HIV-negative partners, suggesting that disclosure by HIV-negative sexual partners of HIV-positive men may be important. Being a user of particular party drugs was associated with recent risk with HIV-negative partners. With partners whose serostatus was unknown, the use of certain party drugs and using substances in the context of sex was associated with risk, possibly as a result of reliance on assumptions of seroconcordance. This same pattern was seen for HIV-positive casual partners. These data have intervention implications for both HIV-positive and HIV-negative men.