The effects of insulin on melanogenesis were examined in human Swift melanoma cells. When these cells were grown in a chemically defined culture medium containing insulin (5 microg/ml), they showed a low pigmentation in association with a high activity of glutathione peroxidase (GPO) and a low activity of tyrosinase. In Eagle's minimum essential medium supplemented with foetal calf serum (EMEM-FCS), the Swift cells showed an intense pigmentation in association with a low GPO activity and a high tyrosinase activity. Modulation of GPO activity with sodium selenite had no effect on melanogenesis variables. In contrast, addition of insulin (5 microg/ml) to the EMEM medium led to a marked decrease in tyrosinase activity (p<0.001) and to a concomitant reduction in the levels of 5-S-cysteinyldopa (p <0.01). These results indicate that insulin inhibits the formation of 5-S-cysteinyldopa and that of melanin via the inhibition of tyrosinase activity.