To clarify the mechanisms of thrombocytopenia observed in patients with chronic hepatitis B treated with interferon. We studied six patients with chronic active hepatitis B who received intramuscular injections of natural interferon-alpha (3 or 5 million IU/ day) for 4 weeks. Peripheral blood platelet counts, bone marrow findings, and platelet kinetics, determined using 111In-labeled platelets, were analyzed. Platelets decreased significantly 1 week after the beginning of treatment and remained decreased until the completion of treatment. The number of nucleated cells and megakaryocytes in bone marrow decreased in three of five patients studied during treatment. The kinetic study showed platelet survival time to be 8.1 +/- 1.3 days (range, 5.8-10.0). One day after platelet injection, platelets accumulated predominantly in the splenic area in all patients, whereas hepatic accumulation was predominant 7 days after injection in three of the six patients. Thrombocytopenia during interferon treatment arises from the inhibition of stem cell proliferation and differentiation in the bone marrow and from the capture of platelets by the liver.