Recent experimental studies suggested that hematopoietic cell proliferation and differentiation are under a neuroendocrine control and that they change in relation to the 24-hour period. Moreover, it has been shown that the pineal hormone melatonin (MLT) plays a role in mediating the influence of the psychoendocrine system and of the lighting conditions on the hematopoiesis. Finally, MLT has appeared to regulate hematopoietic cell growth by influencing apoptosis-related mechanisms. In particular, preliminary studies have shown that the pineal hormone MLT may determine some benefits in blood cell disorders, mainly platelet diseases. On this basis, a pilot phase II study of MLT therapy was performed in patients suffering from persistent thrombocytopenia due to different causes. The study included 14 patients, and thrombocytopenia was due to bone metastatic involvement in 5, hypersplenism in 3, myelodysplastic syndrome in 3, DIC in 1, genetic factors in 1, and Werlhof's disease in the last case. MLT was given orally at 20 mg/day in the evening for 2 months. No MLT-related toxicity occurred. A normalization of platelet number was achieved in 8/14 (57%), and platelet mean number significantly increased on MLT therapy. This preliminary study would suggest that MLT may be effective in the treatment of thrombocytopenia due to different reasons, for which no effective standard therapy is available.