[en] The effects of x-irradiation on aminopyrine demethylation and on aniline hydroxylation in rat liver microsomes were examined in relation to sex difference. The levels of both enzyme activities were higher in male rats than in female rats, but the male enzyme activities were inhibited much more by x-irradiation than the female activities. The amount of cytochrome P-450 and the magnitude of its spectral changes induced by the two compounds were also different in male and female microsomes, as were their sensitivities to x-irradiation. The apparent affinity of the microsomal cytochrome P-450 for substrates decreased after x-irradiation in male rats but not in females. Since the apparent affinity of solubilized cytochrome P-450 for substrates did not decrease after x-irradiation, it is suggested that in the male a conformational change in microsomal membranes containing cytochrome P-450 molecules might take place after x-irradiation