A 67-year-old patient, with primary polymyositis and without previous evidence of liver disease, developed clinical and biochemical features of severe cholestasis 3 months after initiation of azathioprine therapy. Liver biopsy showed cholestasis with both cytological and architectural alterations of interlobular bile ducts. Azathioprine withdrawal resulted after 7 weeks in the resolution of clinical and biochemical abnormalities. It is believed that this is the first reported case of reversible azathioprine-induced cholestasis associated with histological evidence of bile duct injury.