Disulfiram (DSF) and diethyldithiocarbamate (DED) were compared for their protective effects against the testicular toxicity induced by acute exposure to cadmium (Cd) in rats. Rats were injected subcutaneously with CdCl2 [26.7 mol (3 mg) Cd/kg], and 30 min later they were injected intraperitoneally with DSF (0.05-0.5 mmol/kg) or DED (0.1-1 mmol/kg). The treatment with DSF at dose levels of 0.1-0.5 mmol/kg prevented the increases in testicular lipid peroxidation and calcium (Ca) concentrations and the decreases in testicular weight that were observed at 7 d after Cd injection. DED at dosage levels of 0.2-1 mmol/kg likewise reduced Cd-induced testicular toxicity. An increase in testicular iron (Fe) concentrations at 7 d and sterility at 59 d after Cd injection were almost completely blocked by treatment with DSF or DED at the highest doses, but lower doses of DSF or DED were ineffective. These results indicated that DSF, which is metabolized to DED, had a protective effect against Cd-induced testicular toxicity nearly equivalent to DED at approximately one-half the dose.