OBJECTIVE To identify relationships between sexual behavior, drug use, and HIV infection among female injection-drug users (IDUs) recruited in community settings. METHODS Risk analysis of 407 survey questionnaires and matched HIV serologies (n = 403) from female IDUs recruited from community settings in 3 inner-city neighborhoods in San Francisco during 1991 and 1992. RESULTS The HIV seroprevalence of our sample was 11.4%. Fifty-four percent reported using crack cocaine in the past 30 days. HIV seroprevalence was 10.5% among crack cocaine smokers and 12.5% among nonsmokers. In multivariate analysis, HIV infection was associated with a history of sex for money exchanges (adjusted odds ratio [AOR] = 3.11; 95% confidence interval [95% CI] = 1.37, 7.02); history of syphilis (AOR = 3.30; 95% CI = 1.36, 7.99); and African American ethnicity (AOR = 5.31; 95% CI = 2.05, 13.73). Crack smoking in the past 30 days (AOR = 0.33; 95% CI = 0.15, 0.71) and having a current steady sexual partner (AOR = 0.48; 95% CI = 0.24, 0.94) were both inversely associated with HIV infection in the multivariate model. None of our injection-related variables were predictive or protective of HIV infection, when controlled for the above factors. CONCLUSIONS Unprotected heterosexual activity is a principal risk factor for HIV infection among female IDUs in San Francisco. Greater reported sexual risk behavior of crack smokers was not reflected by a higher HIV rate at present, perhaps because of lower prevalence of HIV among their sexual partners.