The sample included 343 opioid-dependent adults enrolled in two national multisite studies of the National Drug Abuse Treatment Clinical Trials Network (CTN001-002). Opioid-dependent individuals were recruited from 12 sites across the United States from January 2001 to July 2002. We examined associations between depressive symptoms, co-occurring substance use (i.e., the use of substances other than opioids), and HIV-related sexual and injection risk behaviors. Data were collected using the Addiction Severity Index and the HIV Risk Behavior Scale, and analyzed using linear regression. Depressive symptoms were associated with an increased level of injection risk behaviors but were not associated with risky sexual behaviors. The co-occurring use of amphetamines also increased the likelihood of risky sexual behaviors. The study limitations and clinical implications are noted. The study was funded by the U.S. National Institute on Drug Abuse.