Simvastatin, recently introduced in clinical practice for pharmacological treatment of hypercholesterolemia, has been found to cause minor and reversible elevations of serum transaminases. We report a case of acute cholestatic hepatitis during simvastatin therapy. Clinical, biochemical, immunological, and histological findings were consistent with a simvastatin-induced liver damage through an immunological-mediated mechanism. This case suggests a careful monitoring of liver function tests during simvastatin therapy, and caution in continuing simvastatin administration when elevations of serum transaminases take place.