A prospective double blind placebo controlled study was conducted on 41 patients with a clinical diagnosis of acalculous biliary pain (ABP) and 10 healthy volunteers. Cholecystokinin (CCK) ( Kabivitrum , Uxbridge ) was given intravenously (1 Ivy Dog Unit/kg) over 5 min in a randomized crossover study using normal saline as a placebo infusion. All referred patients had undergone at least one normal oral cholecystogram, abdominal ultrasound and upper gastrointestinal endoscopy before infusions. Twenty-six patients developed pain in response to the CCK infusion and not the placebo, and the pain did not differ from their spontaneous pre-infusion pain as measured by the McGill Pain Questionnaire and a Visual Analogue Pain Scale. Fourteen patients developed no pain with either infusion, and one developed pain with both placebo and CCK. All patients whose pain was reproduced (CCK-positive) underwent cholecystectomy and peroperative cholangiography. Operative findings were normal in all of the CCK-positive group except one in whom a small common bile duct stone was found. Histopathology of resected gallbladders was abnormal in 24 out of 26 cases, but all patients operated on remained pain-free at follow-up (mean 11 months, range 2-24 months). Repeat CCK infusion postoperatively failed to bring on pain in any of the postoperative group. The CCK infusion test is a simple, cheap, bedside or out-patient procedure which will identify true acalculous biliary pain which will respond well to cholecystectomy.