Sl/Sld mice maintain normal platelet counts in spite of a reduced number of megakaryocytes, but their megakaryocytes are macrocytic. The present studied were done to analyze platelet turnover in the steady state and thrombocytopoietic responses to perturbations of the platelet count. Platelet production, estimated with 35S incorporation in the steady state, blood volume, and total complement of peripheral platelets were normal. Sl/Sld mice responded to thrombocytopenia with normal degrees of macromegakaryocytosis and production of macrocytic platelets, but rebound thrombocytosis did not occur. Their megakaryocytes were unusually responsive to transfusion-induced thrombocytosis, showing a prompt and substantial reduction in size. Platelet turnover was normal in undisturbed Sl/Sld mice, and feedback regulation occurred. However, increased numbers of platelets were not produced in response to stimulation. The findings are consistent with the possibility that their megakaryocytes are large because of stimulation rather than a direct local effect of the abnormal microenvironment.