In addition to its well-known influence on circadian rhythms, melatonin has been described as being able to increase the number of platelets in circulating blood. This provided the rationale to evaluate melatonin for toxicity and efficacy in three patients with idiopathic thrombocytopenic purpura (ITP) refractory to initial treatment with corticosteroids or splenectomy (refractory ITP). Patients received melatonin for 1 month. The therapy was continued for 2 additional months in patients with stable or responding disease. After 3 months, the stable or responding patients continued the therapy for 3 months and more. All patients had a partial response after 1 month. Continuing with the treatment, none of the three patients had disease progression (average follow-up time of 31 months; range: 23-46 months). Toxicity was lacking, with the only side effect being drowsiness. Our experience suggests that melatonin may be safe and effective in patients with refractory ITP.