Objective: To determine the efficacy of morphine enhanced radionuclide cholescintigraphy (MC) in the diagnosis of acute cholecystitis (AC) in critically ill patients. Design: Retrospective chart review. Setting: 2 university hospitals. Patients and methods: Records of all ICU patients who underwent MC as part of an evaluation for AC over an 8 year period were reviewed (n = 45). All patients initially had standard radionuclide cholescintigraphy (RC) performed which showed nonvisualization of the gallbladder (GB) and were then given morphine sulfate (0.05 - 0.1 mg/kg iV). Results: The mean age was 54 years (range 18-84 years). Risk factors for AC included fasting in 41 patients (mean 12.4 days) and total parenteral nutrition in 32 patients. Signs of biliary sepsis included temperature > 100 degrees F in 38 patients, WBC > 10000/ml(3) in 40 patients, abdominal pain in 29 patients, and abnormal liver fuction tests in 42 patients. 23 patients had GB ultrasonography, with 7 showing stones. MC was positive (non-visualization) in 16 patients and negative (GB visualized) in 29, including 4 with gallstones. All patients in whom the GB was visualized did so within 1 h. There were 13 patients with positive MC who underwent operation; 12 had AC (9 acalculous, 3 calculous). Three patients were treated medically and recovered (false positive). All 29 patients with negative MC were true negatives. Overall, MC had an accuracy of 91%, sensitivity of 100%, specificity of 88%, positive predictive value of 75%, and negative predictive value of 100%. Conclusion: MC is a useful test in the evaluation of critically ill patients for suspected AC, particularly in patients with known risk factors or documented gallstones.