Isolated thrombocytopenia occurs frequently in patients infected with HIV. Studies of mechanisms of thrombocytopenia and clinical response to therapy suggest that the thrombocytopenia is often antibody mediated (ITP). The best approach to treatment of these patients is uncertain in that the routine modalities (steroids, splenectomy, vinca alkaloids) that are used to increase the platelet count in patients with classic ITP are known to be immunosuppressive. We report here the results of intravenous gammaglobulin (IVGG) treatment of 22 patients with HIV-related acute and chronic ITP who had severe thrombocytopenia and bleeding symptoms. Only one patient had an opportunistic infection at the time of treatment. Eight patients were homosexual, eight had hemophilia, three were i.v. drug abusers, two children had congenital acquisition of HIV, and one was the wife of an HIV + i.v. drug abuser. The average pretreatment platelet count was 22,000/microliter (hemophiliacs were treated at higher platelet counts than were the other patients), and the mean peak platelet count measured on days 5 to 8 was 182,000/microliter. Nineteen of 22 patients had peak platelet counts greater than 50,000/microliter following IVGG and 17/22 had peak counts greater than 100,000/microliter. After the initial infusions, all but three refractory patients could maintain adequate platelet counts with IVGG alone infused no more often than once every 2 weeks. The outcomes for the 22 patients after multiple maintenance IVGG infusions were remission, 5; stable without therapy, 1; maintenance, 13; and refractory, 3. The eight hemophiliacs with ITP responded better than did the eight homosexual ITP patients; their mean peak platelet count was 227,000/microliter versus 142,000/microliter in the homosexuals. In summary, patients with HIV-related ITP without opportunistic infections responded well to IVGG, with peak platelet counts comparable to those of ITP patients not infected with HIV. IVGG may be a useful therapy of ITP in HIV+ patients, since it appears to be less immunosuppressive than are conventional therapies, and none of the 22 HIV+ patients developed an opportunistic infection while receiving IVGG alone.