Diagnosis of acute cholecystitis in critically ill patients is often difficult; clinical signs are subtle, and radiologic tests are nonspecific and have a high incidence of false-positive results. This study reviews our experience with intravenous morphine sulfate as an adjunct to promote gallbladder filling in 18 critically ill patients who demonstrated nonvisualization of the gallbladder during cholescintigraphy performed as part of a diagnostic workup for occult sepsis. Findings suggestive of a biliary source included fever, leukocytosis, abdominal tenderness, abnormal liver function test results, fasting, and total parenteral nutrition. Morphine was administered to all 18 patients after nonvisualization of the gallbladder; in 17 cases prompt visualization was noted, thus excluding cystic duct obstruction. The remaining patient underwent operation for acalculous cholecystitis. None of the 17 patients whose gallbladders were visualized had a subsequent clinical course consistent with untreated biliary sepsis. Radionuclide cholescintigraphy with morphine appears to be useful in the evaluation of critically ill patients with suspected biliary sepsis. It is particularly helpful in confirming or excluding the diagnosis of acute acalculous cholecystitis in patients who are fasting or receiving total parenteral nutrition and initially demonstrate nonvisualization of the gallbladder and in patients who have previously documented gallstones.