HIV-seropositive opioid-dependent patients maintained on an opiate-agonist who continue to use cocaine and to engage in other high-risk behaviors may benefit from enhanced treatment services; however, there is currently little data to guide the formulation of such services. We report on a preliminary study in which six HIV-seropositive opioid-and cocaine-dependent patients were provided a 12-week comprehensive pharmacologic/psychosocial treatment program developed specifically to meet the treatment needs of HIV-seropositive drug users. This program was comprised of buprenorphine (12 mg/day), bupropion (150 mg/day), and twice weekly manual-guided group therapy. Results showed significant decreases in intravenous cocaine use, cocaine craving, and symptoms of depression. A post-hoc comparison to outcomes of eight HIV-seropositive patients receiving standard methadone-maintenance found no improvements for patients receiving standard care. Controlled investigation of enhanced drug treatment programs for HIV-seropositive patients may be warranted.