Summary Megakaryopoiesis was examined in 10 patients (eight females and two males) with cyclic thrombocytopenia (CT) to investigate the underlying pathogenesis. Numbers of CFU-Meg and megakaryocytes and the mean cytoplasmic area (mean area) of megakaryocytes at the peak, nadir, ascent mid phase, and descent mid phase of the platelet cycle were determined. The patients were classified as female cases group I (cases 1–4; previously diagnosed as ITP and CT occurred during remission), female cases group II (cases 5–8; persistent CT from initial diagnosis), and male CT (cases 9 and 10). In three of the four female cases in group I, numbers of CFU-Meg and megakaryocytes were normal or increased persistently during the platelet cycle, whereas the mean area fluctuated in synchrony with the platelet cycle, suggesting failure of cyclic production rather than platelet destruction. In the female cases in group II and one female case in group I, numbers of CFU-Meg and megakaryocytes were also normal or increased at four phases of the cycle, but the mean area did not fluctuate, remaining large during the cycle, suggesting cyclic destruction or platelet clearance. In contrast, in the male patients values for numbers of CFU-Meg, megakaryocytes and mean cytoplasmic area fluctuated during the platelet cycle, indicating that cyclic changes in megakaryopoiesis generated the platelet cycle. These findings indicate that the measurement of cytoplasmic area is useful for distinguishing cyclic platelet production from cyclic destruction or clearance in CT.