Chronic refractory severe pain in HIV-infected patients is a common and often neglected problem. Little data exist evaluating its epidemiology, clinical features, and treatment. Our study assessed all HIV-infected inpatients referred to the pain control service over a 2-year span. All (24) inpatients with HIV infection with chronic refractory severe pain referred to the pain control service (PCS) over a 2-year period were prospectively followed daily by trained specialists who graded the pain, recommended appropriate therapy, and assessed outcome. Ten surviving patients had further long-term outpatient follow-up. The patients included 14 intravenous drug abusers, five of whom were on methadone maintenance. Localized lower-extremity pain was present in 58%. Pain had been present for ≥1 month in 21 (88%) and for ≥6 months in 12 (50%). No patient had been on pain control around the clock. After PCS consultation, all surviving patients (21 of 21, 100%) had partial or total pain relief within 2 weeks (eight within 1 week) using around-the-clock opioid analgesia adjusted daily as necessary. No differences were seen between substance abusing/methadone patients and others. No significant adverse reactions or new addiction problems were found. Our conclusion is that effective pain control can be achieved using around-the-clock opioid analgesia in terminal HIV-infected patients with severe, chronic, refractory pain even if the patients are substance abusers.