Rat hepatic microsome-catalyzed metabolism of AFB1 (Aflatoxin B1) to AFM1 and AFQ1, and the metabolic activation of AFB1 to DNA-alkylating metabolites in male and female rats of various strains before and after gonadectomyy, and in castrated male and immature female rats treated with testosterone, was studied. It was found that male rats showed about a 2.5-fold greater formation of AFM1, AFQ1 and DNA-alkylating metabolite than females; castration resulted in a decrease in metabolism, whereas ovariectomy had no significant effect on metabolism in the female. Testosterone treatment (4 mg/rat, 3x/wk for 5 wks) enhanced the metabolism of AFB1 in castrated male and the immature female rats. Although all the activities tested, i.e., formation of AFM1, AFQ1, and "metabolic activation", showed a difference between sexes when expressed per mg microsomal protein, this difference was reduced for the formation of AFM1 when the activity was expressed per nmole of cytochrome P-450; however, castration of the male rat, and testosterone treatment of castrated male rats, did produce, respectively, a decrease and an increase, in the formation of AFM1. These results suggest that difference in AFB1 metabolism may be the underlying cause of sex differences in toxicity and carcinogenicity of AFB1 in rats. BIBLIOGRAPHIC REFERENCES: Bernacki, R.J. and Gurtoo, H.L., Differential Inhibition of Rat Liver Sialyltransferase(s) by Various Aflatoxins and Their Metabolites. Res. Commun. Chem. Path. Pharm. 10:681-692, 1975. Paigen, B., Ward, E., Gurtoo, H.L., Minowada, J. and Paigen, K., Distribution of Aryl Hydrocarbon Hydoxylase in Normal Population and in Twins. 4th Annual Carcinogenesis Collaborative Conference, Orlando, Florida, February, 1976, in press.