Pretreatment of rats with repeated i.p. doses of fleroxacin had no effect on the hepatic O- and N-demethylation of p-nitroanisole (PN) and aminopyrine (A) respectively, on the p-hydroxylation of aniline or on the hepatic levels of cytochrome P-450 and protein content. Addition of fleroxacin directly to incubation mixtures reduced PN O-demethylase activity significantly but did not affect the other two oxidative reactions. The N-oxide metabolite increased PN O-demethylation by 16% whereas the N-demethylated metabolite decreased the N-demethylation of A by 10%. Concomitant administration or pretreatment with fleroxacin had no effect on antipyrine's elimination kinetic parameters.