Our objective was to examine the efficacy and toxicity of continuous, low-dose interferon-alpha therapy for human immunodeficiency virus-related immune thrombocytopenic purpura (HIV-ITP) in a Phase II clinical trial overseen by a community-based consortium of physicians conducting clinical trials in HIV-related diseases. Sixteen patients with HIV-ITP defined by prospective clinical criteria were enrolled; the majority had failed other therapies for HIV-ITP. Baseline and serial measurements were made of platelet counts, complete blood counts, serum chemistries, platelet-associated immunoglobulin, and CD4+ T-lymphocyte counts; subjective symptoms and bleeding were recorded. Three million units of interferon-alpha 2b were self-administered by subcutaneous injection every Monday, Wednesday, and Friday for 16 weeks. Thirteen participants were evaluable for response. One obtained a complete response, eight had partial responses, and four had no response to interferon-alpha therapy. The mean absolute platelet count of the group rose from 15.5 x 10(9)/L at baseline to 47.3 x 10(9)/L at 2 weeks and remained in this range for the duration of the study. CD4+ T-lymphocyte counts and serum chemistries did not change significantly during therapy. Ability to detect platelet-associated immunoglobulin did not change in a predictable manner in relation to platelet count response. Hematologic toxicity was limited to one episode of granulocytopenia, which resolved after a lowering of zidovudine dosage. Subjective toxicities were mild and tolerable, and minor bleeding problems improved in all participants so affected. Low-dose, continuous therapy with interferon-alpha resulted in meaningful increases in the platelet counts of the majority of study participants with HIV-ITP. Interferon-alpha was safe and tolerable for most participants with HIV-ITP at the dosage and schedule employed in this study. Interferon-alpha for clinically significant thrombocytopenia and who have failed to respond to zidovudine.