Both in vitro and in vivo effects of lithium on mouse hematopoiesis were investigated. The addition of 1 mmol lithium carbonate to the culture enhanced in vitro colony formation of the granulocyte macrophage precursor (CFU-GM) by 26%, the megakaryocyte precursor (CFU-Meg) by 29%, and the erythrocyte precursor (CFU-E) by 46% as compared to the control culture without lithium carbonate. Lithium resulted in an increase of colony size for both the CFU-Meg and the CFU-E. Oral administration of lithium chloride at daily doses of 0.3 mg caused a significant increase in granulocytes 3 to 12 days after the start of administration. It also resulted in a mild elevation of the platelet count, but it had no influence on hematocrit. The number of the CFU-GM increased transiently on day 3 of the lithium administration and subsequently returned to the pretreatment level. Furthermore lithium accelerated the recovery of the granulocyte count and bone marrow CFU-GM content after 300 rad total body X ray irradiation.