We report two cases of acalculous cholecystitis due to infection with cytomegalovirus (CMV) and cryptosporidium. Both involved homosexual men who presented with right upper quadrant pain and elevations of serum alkaline phosphatase and bilirubin. Cholecystectomy specimens showed a thickened gallbladder wall and ulcerated mucosa. There were no stones. CMV inclusion bodies were found in granulation tissue at the base of ulcers and intact mucosa surrounding ulcers. Cryptosporidia were aligned along the luminal surface of intact mucosal epithelial cells. Both organisms have a patchy distribution; hence the diagnosis requires a high degree of suspicion. The prognosis is poor. Following cholecystectomy, both patients pursued a downhill course with development of pancreatitis and cholangitis. Both patients are now dead.