Using the technique of thrombophoresis (TP), platelet and megakaryocyte dynamics following acute thrombocytopenia were studied in two normal subjects during periods of ethanol ingestion and abstinence. Thrombocytopenia was induced over a period of 12 hr. A logarithmic decline in platelet count during TP and the serial morphologic changes in megakaryocytes during recovery from thrombocytopenia are described. Although these parameters were not affected by ethanol ingestion, platelet counts after TP did not return to normal until ethanol was discontinued. 51Cr-labeled platelet survival was normal in one subject studied, and no evidence of increased platelet sequestration was found. It is concluded that heavy ethanol ingestion induces, augments, or sustains thrombocytopenia by impairing megakaryocytopoiesis in man. The mechanism by which ethanol induces thrombocytopenia may be due, in part, to “ineffective thrombopoiesis,” impairment of the differentiation of precursor cells into the megakaryocytic compartment, or a combination of these factors.