The influence of vitamin A on the acute oral toxicity of hexachlorocyclohexane (HCH) was investigated in male albino rats. Rats were fed a synthetic diet free of vitamin A or containing vitamin A at 2000 or 10 ~ 1. U./kg for 12 weeks. The hepatic vitamin A contents of the three diet groups of rats were markedly different at the end of the week 9, when very mild signs of deficiency were noticed only in the rats fed the vitamin A-free diet. The acute oral toxicity of HCH determined at the end of week 9 of feeding on the basis of lethal dose 10, lethal dose 50, and lethal dose 90 values, and signs of toxicity and serum and liver levels of the marker enzymes of toxicity revealed greater susceptibility of the vitamin A-deficient rats to HCH toxicity. Assay of the activities of hepatic xenobiotic metabolizing enzymes showed slight-tomoderate decreases in specific activities of cytochrome P-450, N-demethylase, f3-glucuronidase, and glucuronyl transferase in the vitamin A-deficient rats, though the activity of glutathione S-transferase was slightly higher in them compared with those of the supplemented rats. The results suggest the possibility that the greater susceptibility of the vitamin A-deficient rats to HCH toxicity could be due to the impaired detoxification of HCH, as inferred from the reduced activities of the hepatic microsomal enzymes of detoxification in these rats. Also, vitamin A supplementation, particularly in excess, but not at hypervitaminotic levels, is protective in the rats against HCH toxicity, possibly due to the more efficient detoxification of the chemical.