We examined the associations of cocaine use with HIV/sexually transmitted diseases (STDs) in a sample of 184 soup kitchen attendees using a mobile medical van in Manhattan (male = 66%; black or Hispanic = 81%; cocaine use, primarily crack = 75%; ever injected drugs = 22%). In addition to confirming the association between years of cocaine use and HIV antibodies in this sample (odds ratio [OR] = 2.11;p< .05) we examined thepatternof associations of cocaine use and non-HIV STDs under the hypothesis that the strength of an association depends on the efficiency of sexually transmitting a particular STD (high, moderate, and low for syphilis, hepatitis B and hepatitis C, respectively). As predicted, years of cocaine use was strongly associated with syphilis (OR = 2.07;p< .05), moderately associated with hepatitis B core antibodies (OR = 1.50;p< .05), and not significantly associated with hepatitis C antibodies (OR = 1.48;p> .05). A reverse pattern of associations between opiate use (injection drug use) and the three STDs points to the singular significance of cocaine use in the sexual transmission of STDs, and by inference, HIV. This conclusion is further bolstered by correlations of biologic (hair assays) and self-reported measurements of cocaine use (but not opiates) with self-reports of high risk sexual behavior among the women (number of partners and selling sex) and men (number of partners and buying sex). These data underscore the need for effective cocaine treatment and HIV interventions tailored to the large numbers of cocaine users in inner cities.