Although a major regulator of thrombocytopoiesis is the number of circulating platelets, several observations suggest that independent alternative regulatory mechanisms may exist. In some situations there is a curious association of megakaryocytopenia and megakarocytic macrocytosis in spite of normal platelet counts. If macrocytosis is considered as a sign of stimulation, this association suggests a cause and effect relationship between decreased numbers and increased size of megakaryocytes. This thesis was tested by examining the delayed effects of sublethal irradiation and the acute effects of hydroxyurea in mice. It was found that megakaryocytopenia and macromegakaryocytosis occurred together and that platelets counts were either normal or only slightly reduced. Therefore it was concluded that normal numbers of platelets could be produced by decreased numbers of megakaryocytes. Megakaryocytopenia appeared to be compensated, in part, by increased size of megakaryocytes, but the mechanism by which this occurred has not been elucidated. It is postulated that a reduction in the number of cells of the megakaryocytic system is sensed by a homeostatic mechanism that then acts to stimulate the cells that are present. This stimulation may then be manifested as macrocytosis of megakaryocytes.