OBJECTIVE To test the hypotheses that: 1) postprandial gallbladder emptying might be abnormal in patients with acalculous biliary colic; and 2) that hymecromone, a drug that increases bile flow and relaxes biliary muscle might improve symptoms. METHODS Twenty-four women were studied. Twelve patients presented recurrent biliary type of pain in the absence of gallstones, and persistence of contrast in the gallbladder, 24 hours after an oral cholecystogram, suggesting cholesterolosis. Twelve healthy volunteers used as controls had no symptoms and the gallbladder was not visible the day after an oral cholecystogram. Gallbladder emptying induced by an oral meal was studied with ultrasound in both groups before and after the administration of hymecromone. RESULTS Gallbladder volumes were similar in both groups (23 +/- 10 ml vs. 31 +/- 11 ml; NS). Gallbladder emptying in the control group was simple exponential (R2 = 0.948 +/- 0.059) with a rate of 32 +/- 16 minutes. Gallbladder emptying was bimodal in patients. Gallbladder volume increased to 120% in the first 10 minutes, to empty exponentially thereafter (R2 = 0.964 +/- 0.040. Rate: 29 +/- 22 minutes). This resulted in a marked reduction in gallbladder volume emptied at 40 minutes when compared to controls (30% +/- 27% vs. 54% +/- 14%; p = 0.012). Pretreatment of controls with hymecromone induced an emptying pattern similar to that of patients. In patients, emptying after hymecromone did not change but symptoms were improved. CONCLUSIONS An abnormal emptying pattern of the gallbladder was identified in patients with acalculous biliary colic, and hymecromone was partly effective to reduce pain, despite a minor effect on gallbladder emptying pattern.