This study randomized 90 HIV-seropositive, methadone-maintained injection drug users (IDUs) to an HIV Harm Reduction Program (HHRP+) or to an active control that included harm reduction components recommended by the National AIDS Demonstration Research Project. The treatment phase lasted 6 months, with follow-ups at 6 and 9 months after treatment entry. Patients in both treatments showed reductions in risk behaviors. However, patients assigned to HHRP+ were less likely to use illicit opiates and were more likely to adhere to antiretroviral medications during treatment; at follow-up, they had lower addiction severity scores and were less likely to have engaged in high risk behavior. Findings suggest that enhancing methadone maintenance with an intervention targeting HIV-seropositive IDUs increases both harm reduction and health promotion behaviors.