We studied a male patient with cyclic thrombocytopenia whose bone marrow megakaryocyte count showed cyclic fluctuations in synchrony with cyclic changes of platelet count. He failed to respond to either prednisolone or bolus methylprednisolone therapy, but subsequently he was successfully treated with azathioprine. To investigate the underlying pathogenesis of the cyclic fluctuations in the platelet count. we studied the kinetics of megakaryocyte progenitor cells (CFU-Meg) and the effects of the patient's peripheral blood mononuclear cells on CFU-Meg. In one cycle of the platelet fluctuation, the increase in the CFU-Meg number preceded an increase in the bone marrow megakaryocyte count and then the platelet count. In the latter half of the cycle, CFU-Meg, bone marrow megakaryocytes and platelets began to decrease in that order. Peripheral blood mononuclear cells obtained from the patient in the thrombo-cytopenic phase suppressed megakaryocyte colony formation from normal bone marrow cells in a dose-dependent manner. In contrast, these cells obtained in the phase of a normal platelet count did not suppress megakaryocyte colony formation at all. These findings indicate that the cause of platelet fluctuation is periodic failure of megakaryocytopoiesis at the stage of CFU-Meg and that the patient's peripheral mononuclear cells are responsible for periodically suppressing the CFU-Meg.