Injection risk practices and unprotected sex between injection drug users (IDUs) and their sexual partners are responsible for a high proportion of AIDS cases and new HIV infections in the United States. The purpose of this study was to investigate the links between drug use behaviors and psychosocial factors with high-risk sexual behaviors among male and female IDUs. Understanding the determinants of sexual risk practices among drug users can lead to the development of more effective programs to prevent sexual HIV and STD transmission. This study enrolled a community sample of 101 IDUs (males = 65, females = 36), primarily African American and unemployed, who injected drugs and had unprotected sex in the past 3 months. The sample was categorized into highest sexual risk (multiple partners and intercourse without condoms) and lower sexual risk subgroups. Univariate analyses showed that IDUs at highest sexual risk had lower sexual risk reduction self-efficacy (p =.01) and were more likely to be African American (p =.02). Drug users at highest sexual risk also used noninjected cocaine and crack more frequently (p =.05), were less likely to inject heroin (p =.04), and tended to more often inject cocaine (p =.05). IDUs at highest sexual risk also tended to more often use crack and methamphetamines. Logistic regression analyses showed that injecting cocaine or crack, sexual risk reduction self-efficacy, and race were independent predictors of sexual risk behavior levels. Sexual risk reduction programs for this population are needed, with HIV prevention programs tailored to specific IDU risk reduction needs.