Besides its effect in inhibiting proliferation and inducing differentiation of HL-60 cells to macrophage-like cells, TPA also produces a transient increase of transplasma membrane redox activity and pyridine nucleotide levels and a shift in the NAD+/NADH ratio. After 24 h of incubation NADH ferricyanide reductase activity of isolated plasma membranes was significantly higher than that of plasma membrane from non-differentiated cells. This correlated with the enhanced short-term oxidation of NADH in response to ferricyanide by HL-60 cells incubated with TPA for 24 h. Since differentiated cells with similar levels of NADH showed different redox activities, the redox chain itself seems to be modulated during differentiation induced by TPA.