Female adult Wistar rats were treated with single or repeated doses of ketoconazole ranging from 10 mg/kg to 100 mg/kg. Single dose treatment produced inhibition of hepatic microsomal ethoxyresorufin O-deethylation (EROD) and aldrin epoxidation (AE) 2 hr after oral dosing. Twenty-four hours after a single dose, inhibition was still demonstrable after the low dose of 10 mg/kg, but at higher doses increased microsomal activity was apparent. After 7 days repeated dosing liver weight and microsomal protein content were increased in a dose-dependent fashion. EROD and AE were induced at all doses after repeated treatment when the increase in liver size was considered. These effects were seen at doses within the antimycotic therapeutic range and add support to the suggestion that reported drug interactions with ketoconazole in man are due to the effects of this drug on hepatic microsomal activity.