A 45-minute infusion of an octapeptide of cholecystokinin (Kinevac; Squibb Diagnostics, New Brunswick, NJ) was used to measure the gallbladder ejection fraction during cholescintigraphy in 40 normal volunteers. Cholecystokinin cholescintigraphy was shown to be a reproducible test. The maximum mean gallbladder ejection fraction occurred 15 minutes after cholecystokinin infusion and was 74.5% +/- 1.9% (mean +/- SEM). A gallbladder ejection fraction greater than 40% (mean -3SD) was arbitrarily defined to be normal. The gallbladder ejection fraction test was then used to identify patients with acalculous biliary symptoms who may respond to cholecystectomy. A total of 103 patients was tested; 21 had abnormal gallbladder ejection fractions and were randomized into two groups, cholecystectomy or no operation. These patients were followed up symptomatically at 3-month intervals for 13-54 months (mean, 34 months). Of the 11 patients who underwent cholecystectomy, 10 (91%) lost their symptoms and 1 improved. Of the 10 patients in the group that did not undergo surgery, all continued to be symptomatic, 2 of whom requested cholecystectomy after 13 and 24 months, respectively. Of the 13 gallbladders obtained from surgery, 12 showed evidence of chronic cholecystitis, muscle hypertrophy, and/or narrowed cystic duct. A normal gallbladder ejection fraction was recorded in 82 patients, and further treatment was left to the discretion of their referring clinician. On follow-up, 50 patients were asymptomatic and 10 were symptomatic without specific treatment of the biliary tract; 14 underwent cholecystectomy, 8 of whom were asymptomatic. Pathological abnormalities were recorded in 6 of the removed gallbladders. It is concluded that the gallbladder ejection fraction obtained after a 45-minute infusion of cholecystokinin during cholescintigraphy is a reproducible measure of gallbladder emptying, and that cholecystectomy alleviates the biliary-type pain of patients with a reduced gallbladder ejection fraction.