A B S T R A C T Incorporation of 'selenomethionine ('SeM) has been used to study platelet production in rabbits. Radioactivity of platelets was low after the intravenous administration of 'SeM and rose to a maximum approximately 3 days after administration. Platelet radioactivity was independent of concurrent plasma levels. The life span of rabbit platelets, as estimated with this technique, was 4-5 days. In vivo reutilization of '7SeM previously incorporated into plasma proteins was not detected. In vitro incorporation of 'SeM by platelets in platelet-rich plasma was not demonstrated.Acute hemorrhage 24 hr before administration of 'SeM increased the incorporation of 'SeM into platelets. Transfusion-induced thrombocytosis reduced the incorporation of 'SeM to approximately 30% of that observed in control animals. Suppression of bone marrow function with nitrogen mustard resulted in decreased numbers of platelets in the circulation, and a decrease in incorporation of 'SeM. Delayed appearance of '7SeM was observed in circulating platelets during recovery from marrow suppression. Injection of 75-225 ml of plasma from thrombocytopenic donors into normal rabbits increased incorporation of 'SeM into platelets while normal plasma did not have this effect.The rate of appearance of 'SeM in circulating platelets appears to provide a sensitive and specific method for the study of production of platelets by megakaryocytes. The data suggest more rapid entry of platelets into the circulation, and a sustained increase in incorporation of 'SeM into platelet protein after stimulation of platelet production. The results are consistent with the concept of a humoral agent (thrombopoietin) that acts on megakaryocytes to regulate platelet production.