Injecting drug users (IDUs) play a prominent role in the transmission of human immunodeficiency virus (HIV), particularly in urban areas such as New York City, where they comprise nearly half of all adult acquired immunodeficiency syndrome (AIDS) cases. Intervention studies have demonstrated that IDUs are responsive to safer sex messages, but sexual behavior appears to be more resistant to change than drug use behavior. This multidisciplinary study (without an intervention component) assesses changes in sexual risk behavior as a function of time, HIV status, and disease progression in a cohort of HIV+ and HIV- male IDUs (N = 144) for 4 years. RESULTS For HIV+ and HIV- men, there were increases in abstinence and monogamy, with decreases in the frequency of unprotected vaginal/anal sex and sexual risk index scores. With the exception of monogamy, HIV+ men reported lower levels of risk. Although there was also a decline in substance use, this accounted for only some of the decline in sexual risk behavior. Among the HIV+ men, a CD4 level below 200 was associated with more abstinence and monogamy. HIV-related medical symptoms were associated with increased abstinence, less unprotected sex, and lower sexual risk index scores. Lower neuropsychological memory test scores were associated with increased abstinence and lower sexual risk index scores. Neurological impairment and depression were not associated with sexual risk behavior. CONCLUSIONS IDU men in New York City have modified their sexual behavior toward safer practices. Lower levels of risk are found among HIV+ men, particularly those with more progressed HIV illness. Nevertheless, a substantial amount of sexual risk behavior remained in this cohort, indicating the continued need for education and intervention.