The human promyelocytic leukemia cell line, HL-60, was used to investigate the effects of lithium on dimethyl sulfoxide (DMSO)-induced granulocytic differentiation of these cells. Dose-response studies showed an optimal increase of cellular proliferation when cells were incubated with 5 mM lithium for 5 days (127 +/- 5% of DMSO only treated cells). This enhancement in growth was preceded by significantly increased [methyl-3H]thymidine incorporation (143 +/- 4% of DMSO only treated controls) after 2 days. However, no significant changes in the ability of cells to reduce NBT could be detected irrespective of whether the cells were incubated with 1.25% (v/v) DMSO only, or with DMSO plus non-toxic concentrations (less than or equal to 10 mM) lithium. From the results obtained it would appear as if the arrest of growth induced by DMSO and the stimulation of proliferation effected by lithium occurs along independent pathways and that lithium exerts its mitogenic effect prior to the onset of terminal differentiation initiated by DMSO.