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Objective. The objective of the present study was to examine gender differences and other factors associated with current heroin and cocaine use among middle-aged drug users.Baseline data were merged from 2 studies of men and of women with or at risk for HIV infection. Analysis was restricted to study participants who had ever used heroin or cocaine and who were 49-60 years of age at the time that they were interviewed. HIV-antibody status, drug-use history, and psychosocial and sociodemographic data were examined. Logistic regression models were used to assess factors independently associated with current heroin and cocaine use.Of 627 persons who ever used heroin and/or cocaine, 250 (39.9%) reported using these drugs within 6 months of the study interview conducted at baseline. Men were more likely to be using drugs currently, compared with women (42.3% vs. 28.2%; P = .007). In multivariate analysis, men, unemployed persons, and HIV-seronegative persons were more likely to be using heroin or cocaine at the time of the interview. In addition, current marijuana users, persons drinking alcohol on a daily basis, and persons who had been homeless in the 6 months before the interview were also more likely to be using these drugs.A relatively high proportion of middle-aged substance users with or at risk for HIV infection, especially men, may continue to use illicit drugs into the sixth decade of life. The differences noted between men and women who have used heroin and/or cocaine at some point in their lives suggest that special attention be given to aging and gender issues in framing HIV-prevention and drug-treatment programs.