The administration to the rat of the inhibitors of microsomal mixed function oxidase, SKF 525A and Oxine-5-sulphonic acid (OSA) caused a significant decrease of the hepatic aminopyrine N-demethylase activity, as well as an increase in the plasma levels and antipyretic activity of orally administered aminopyrine. The plasma concentrations of the aminopyrine metabolite 4-aminoantipyrine were reduced in SKF 525-A treated animals while they were slightly increased in those pretreated with OSA. These findings suggest that the in vivo changes of aminopyrine disposition and activity brought about by SKF 525-A were the result of an inhibited hepatic drug metabolism, while the effects produced by OSA were due to a more rapid intestinal absorption of aminopyrine.