Hypertransfusion can enhance myeloid recovery after bone marrow depletion, but its influence on thrombopoietic recovery has not been previously defined. We have studied the pattern of platelet and megakaryocyte recovery in mice hypertransfused after receiving 350 rad whole body irradiation. The platelet counts of the hypertransfused group showing an initial fall due to hemodilution in the expanded blood volume and then fell to a lower nadir than that of the control mice. The rate of platelet recovery was more rapid in the hypertransfused mice. Bone marrow megakaryocyte concentrations in both groups showed a degenerative phase, abortive rise, and regenerative phase. The decrease in megakaryocytes was the same in both groups. The hypertransfused mice showed a greater abortive rise in megakaryocyte concentration preceded by the appearance of a greater number of large megakaryocytes in the bone marrow. However, the most striking effect of hypertransfusion was on megakaryocyte recovery. Although the time of onset of recovery was not different, the rate of recovery was approximately twice as rapid in the hypertransfused group. Administration of daily erythropoietin to hypertransfused mice abolished this more rapid recovery. Thus, the presence of a simultaneous demand for erythroid precursors does affect the rate of megakaryocyte regeneration. Just as the more rapid recovery of granulopoiesis following hypertransfusion may be clinically beneficial, the more rapid reconstitution of thrombopoiesis may also offer clinical advantage in some circcumstances.