The aim of this study was to determine whether an oral administration of melatonin, a known antioxidant, free radical scavenger and metal chelator, influences tissue accumulation and toxicity of cadmium (Cd) in mice exposed subchronically to the metal. The animals received drinking water containing 50 microg Cd/mL only or with additional 2, 4 or 6 microg/mL melatonin for 8 weeks. Melatonin co-treatment brought about a dose-dependent decrease in the renal, hepatic and intestinal Cd concentrations, and the renal and hepatic metallothionein levels followed a pattern similar to that of the Cd accumulation. Histopathological changes occurred only in the kidneys (glomerular swelling and focal tubular degeneration) in all mice from the Cd alone group. In mice co-treated with melatonin, only slight (2 microg/mL melatonin) or no damage (4 and 6 microg/mL melatonin) was seen. The Cd and melatonin treatments did not affect renal lipid peroxidation and iron concentration. These data indicate that orally administered melatonin together with Cd reduces tissue accumulation of this metal; in particular, the reduction of renal Cd accumulation by melatonin is probably responsible for the prevention of Cd-induced injury in this organ.