The diagnostic accuracy and clinical impact of 99Tcm hepatic iminodiacetic acid (HIDA) imaging with cholecystokinin (CCK) was investigated in a prospective study of 359 patients over an 11 year period. All patients presented with right upper quadrant biliary type pain and had a normal ultrasound investigation prior to imaging. CCK was administered as a 3 min infusion at peak gallbladder uptake of HIDA. A gallbladder ejection fraction (GBEF) was used to quantify the gallbladder response to CCK. Two hundred and forty-four of 359 (68%) patients had an abnormal GBEF (< or = 35%). One hundred and thirty-four of 141 (95%) patients who underwent cholecystectomy had abnormal surgical/histological findings and/or relief of symptoms on long-term (mean 5.7 years) follow-up. Clinical follow-up, mean of 5.9 years, of the patients with GBEF > 35% showed 73/79 (92%) of them with little evidence of gallbladder disease. For a total 261 patients with mean clinical follow-up of 5.7 years the sensitivity of GBEF measurement is 95%, specificity is 92% and overall accuracy is 94%. It is concluded that 99Tcm-HIDA imaging, with a 3 min infusion of CCK, is a highly accurate technique and valuable in the diagnostic management of patients with suspected acalculous gallbladder disease.