Pretreatment of male and female rats with cimetidine decreased the amount of 3-hydroxymethylantipyrine in the 24-hr urine, but urinary antipyrine and 4-hydroxyantipyrine were increased compared to that of the corresponding control rats. On the other hand, the amount of norantipyrine and the total amount of antipyrine and its metabolites were not changed by cimetidine, ranitidine and famotidine. These data suggest that ranitidine and famotidine have little effect on the microsomal mixed function oxidase system in male and female rats.