We present the case of a female patient in whom acute hepatitis developed after 180 days of ketoconazole administration (200 mg/day). A prompt renewed hepatic injury after an unintentional rechallenge 6 months later provided definitive evidence for a causative relationship between ketoconazole and acute liver disease. The clinical and biochemical parameters of the case are reported. Histological examination revealed the picture of acute hepatitis with possible transition to chronicity. A prominent accumulation of perisinusoidal lipocytes (Ito cells) was observed.