Purified bacterially synthesized recombinant murine leukemia inhibitory factor (LIF) was injected in varying doses for up to 2 weeks into adult DBA/2 and C3H/HeJ mice. At high doses (2 micrograms, three times daily) LIF exhibited toxic effects seen as behavioral changes, loss of body fat, and thymus atrophy. Dose-related rises were observed in blood platelets, erythrocyte sedimentation rates, and serum calcium to albumin ratios, including dose schedules with no toxic effects. LIF induced a decrease in bone marrow cell numbers, particularly in marrow lymphocytes, and a moderate increase in spleen weight with a reduction in spleen lymphocytes and an elevation of erythroid populations. LIF- injected mice showed a rise in megakaryocytes up to twofold in the marrow and fivefold in the spleen, with an associated 10-fold rise in megakaryocyte progenitor cells in the spleen. Comparable rises in other types of progenitor cells were also observed in the spleen. The observed changes indicate the biologic activity of LIF in vivo and are consistent with the known wide range of in vitro actions of this molecule. The ability of LIF to elevate megakaryocyte and platelet levels suggests a potential clinical application of LIF in the treatment of thrombocytopenias.