Two sublines of a human promyelocytic cell line, HL-60, were used to study the effect of lithium on TPA (12-o-tetradecanoylphorbol-13-acetate) induced macrophage-like differentiation. Although these sublines, HL-60 M and HL-60 JE, had different growth rates, both showed enhanced proliferation when treated with 5 mM lithium (128 +/- 2 and 141 +/- 1% in comparison to controls after 5 days of incubation, respectively). Treatment of the sublines with TPA for 72 h resulted in macrophage-like differentiation (assessed by cell adhesion) of about 90% at 10 nM TPA in HL-60 JE, whereas a maximum of 50% at 100 nM TPA was obtained in HL-60 M. Differentiation was also confirmed by non-specific esterase activity. However, incubation of both sublines with TPA and 5 mM lithium revealed that lithium has little or no effect on the macrophage-like differentiation of the HL-60 cell line.