Human immunodeficiency virus (HIV)-related thrombocytopenia has been well described and requires therapy in about one half of the patients. Conventional modes of therapy with prednisone, danazol, immunoglobulin, and/or splenectomy have not been uniformly successful. We have administered zidovudine to three patients with HIV-related thrombocytopenia. All three patients responded with a sustained increase in their platelet counts, despite discontinuation of conventional therapy. Interruption of zidovudine therapy was associated with a decrease in platelet count. Concomitant with the elevation in platelet count with zidovudine therapy, there was a reduction in the circulating p24 antigen levels. Whether the elevations in the platelet count in these patients with HIV-related thrombocytopenia is due to the antiviral effect of zidovudine is unknown. It is clear that further studies examining the prospective use of zidovudine in the treatment of HIV-related thrombocytopenia are indicated.