We studied the effect of lithium on normal marrow hematopoiesis by determining the numbers of pluripotential (CFUS) and committed stem cells (CFUC, CFUE and BFUE) after in vitro and in vivo exposure to lithium. In the presence of 1 meq/L lithium in vitro, marrow CFUS and CFUC were increased; higher concentrations (greater than or equal to 5 meq/L) were inhibitory. Marrow CFUE and BFUE were decreased at concentrations of lithium greater than or equal to 0.5 meq/L. In vivo (0.5-5.0 meq/L i.p.), lithium produced similar results to those obtained in vitro with striking CFUC enhancement. Serum from these lithium-treated mice contained increased colony stimulating factor (CSF). In the Dexter continuous marrow culture system, lithium stimulated increased CFUC production from the non-adherent fraction. These in vitro nd vivo studies document lithium's ability to modulate hematopoiesis by influencing pluripotential and committed stem cell proliferation and differentiation towards granulopoiesis, apparently at the expense of erythropoiesis. Mechanisms of this modulation are discussed.