We have previously demonstrated that lithium (Li) is an effective agent in accelerating the recovery of granulopoiesis following sublethal (2 Gy) whole body irradiation. In this report, studies are described that further define this Li-mediated recovery by measuring the levels of colony-stimulating factor (CSF) present in serum from mice administered 105 micrograms/mouse (total dose) of ultra-pure Li2CO3 for 3 days immediately following irradiation. On days 1-28 following the last lithium dose, the serum was tested for its CSF activity against both normal non-adherent derived bone marrow target cells and non-adherent marrow cells from mice administered cyclophosphamide (200 mg/kg body weight). Serum was assayed at 0.01, 0.1, 1 and 10 per cent final concentration. No significant difference in the total number of CFU-GM was observed from normal marrow using either serum from irradiated mice or lithium-treated and irradiated mice, although the irradiation did produce a 300 per cent rise in CFU-GM colonies compared to normal serum (days 4 and 10-15). From regenerating marrow, we observed a significant difference (P less than or equal to 0.01) in CFU-GM cultured with serum at 0.1 per cent concentration from irradiated and lithium-treated mice compared to irradiated mice without lithium. The presence of CSF was confirmed by its reduced activity in the presence of anti-(CSF). These results suggest (Li) may increase the sensitivity of CFU-GM to CSF, thereby producing more CFU-GM ultimately providing more circulating granulocytes.