Griseofulvin was fed to male Swiss albino mice, which were sacrificed at varying times after the initiation of the feeding. The following were compared with mice fed a control diet: hepatic histology, hepatic weight, plasma glycocholate, glycolithocholate, cholesterol, bilirubin, and alkaline phosphatase. Concurrent with the development of hepatic protoporphyria, a progressive cholestatic lesion was produced with marked bile canalicular dilatation and elevation of the plasma bile salts, alkaline phosphatase, and cholesterol without a rise in bilirubin. Adaptation to the cholestatic injury occurred in about 60 days despite continued griseofulvin feeding. This was evidenced by decreased values in the biochemical profile with concomitant improvement in the bile canalicular morphology. Following this event of adaptation, Mallory bodies began to appear in the livers, often in the periphery of the hepatic lobule. This model may be useful in studying mechanisms of cholestasis, Mallory body formation, and their relationship to altered microtubular systems in the hepatocyte.