We report the first case of acute cholecystitis due to indinavir-induced cholelithiasis in a patient infected with human immunodeficiency virus who had been receiving indinavir for 56 months. Infrared spectroscopy demonstrated that the gallstone was composed of indinavir monohydrate (50%), calcium bilirubinate (28%), calcium palmitate (10%), cholesterol (7%), and proteins (5%). The role of high-level chronic unconjugated hyperbilirubinemia coupled with high blood concentrations of indinavir is discussed.