Garlic oil, onion oil and one of its constituents, dipropenyl sulfide, all increase, to diverse degrees, glutathione (GSH) peroxidase (GSH:H2O2 oxidoreductase, EC 1.11.1.9) activity in isolated epidermal cells incubated in the presence or absence of the potent tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA). The stimulatory effects of these oils on epidermal GSH peroxidase activity are concentration-dependent and long-lasting, and thus, abolish totally the prolonged inhibitory effect of TPA on this enzyme. Moreover, garlic oil (5 micrograms/ml) inhibits by about 50% TPA-induced ornithine decarboxylase (ODC, L-ornithine carboxy-lyase, EC 4.1.1.17) activity in the same epidermal cell system. This concentration of garlic oil also increases remarkably GSH peroxidase activity and inhibits ODC induction in the presence of various nonphorbol ester tumor promoters. Since the same oil treatments inhibit dramatically the sharp decline in the intracellular ratio of reduced (GSH)/oxidized (GSSG) glutathione caused by TPA, it is suggested that some of the inhibitory effects of garlic and onion oils on skin tumor promotion may result from their enhancement of the natural GSH-dependent antioxidant protective system of the epidermal cells.