Treating patients with HCV-associated thrombocytopenia is a problem, because the pathogenesis of thrombocytopenia is still unclear. We evaluated the clinical and haematological response to leucocyte interferon-alpha in 20 naive patients with chronic hepatitis C and thrombocytopenia (platelet count <140 x 10(9)/l for at least six months) without portal hypertension and/or hypersplenism. They were treated with leucocyte interferon-alpha (3 MU three times per week) for 12 months and followed up for 12 months. Biochemical (ALT) and virological (HCV-RNA) responses were determined. Two patients discontinued treatment because of hyperthyroidism. Of the 18 patients who completed treatment, 12 (66%) showed a biochemical response, 10 of whom (55.5%) also showed a virological response. At the end of follow-up, four patients (22%) showed a complete (biochemical and virological) response. During treatment, platelet counts decreased to less than 10-20% of pretreatment values in most patients. Three of the four patients with a complete response showed a platelet increase during treatment and throughout the follow-up period. In HCV-associated thrombocytopenia leucocyte interferon-alpha is well tolerated and in cases of sustained virological inhibition is able to ameliorate the disease by increasing the platelet count.