Cyclohexylamine hydrochloride has been given in the diet to mice and to Wistar and DA rats for 13 weeks, to provide a constant intake of 400 mg of the base/kg/day. Significantly decreased food intake and body weight gain were found in both strains of rats but not mice. The metabolism of [14C]cyclohexylamine was widely different in Wistar and DA rats and in rats and mice, and these differences were not altered appreciably by chronic intake for 13 weeks. The differences in metabolism resulted in marked and persistent differences in the concentrations of the hydroxylated metabolites in the plasma and testes of treated animals with Wistar much greater than DA much greater than mice. After 7 and 13 weeks testicular atrophy was demonstrated in both strains of rats given cyclohexylamine diet by a decrease in organ weight and by histological changes. DA rats appeared more sensitive to testicular toxicity from cyclohexylamine than Wistar rats, while mice showed no evidence of testicular damage. These data show that the development of testicular toxicity is not related to the extent of hydroxylation. The concentrations of cyclohexylamine in the plasma and testes of the treated animals were lower in mice than in either strain of rats despite a similar daily intake. This suggests that species differences in pharmacokinetics may contribute to the apparent difference in sensitivity to testicular toxicity.