Although the ultrasonic detection of gallbladder sludge is relatively frequent, its clinical importance remains unclear, partly because of the paucity of reliable investigations regarding its natural course in patients without stones. In a retrospective study we investigated the course and clinical significance of gallbladder sludge in patients without stones or other identified gallbladder abnormalities. The diagnosis of gallbladder sludge was made by ultrasound scan in 286 (1.7%) of 17,021 patients. The mean follow-up period for these patients was 20.3 11.5 mo. Of this group 56 patients were without both stones and sludge at the initial examination, and gallbladder sludge developed after a mean observation period of 11.2 -C 10.6 mo. Within 2.0 & 3.5 m o after sludge detection, 40 (71.4%) patients were free of sludge and showed normal gallbladder findings. Gallbladder stones without sludge persistence developed in five patients (8.9%) within 2.5 f 0.6 m o after diagnosis of sludge, and gallstones with persistence of sludge developed in two other patients (3.6%) after 6.1 and 30.7 mo, respectively. In no cases did the stones become clinically symptomatic in the course of the follow-up period. Acute acalculous cholecystitis developed in four patients (7.1%) from 6.5 to 37.5 mo after the first examination. In five patients, sludge persisted after a mean 22.3 * 13.5 mo of follow-up. Although our data show that gallbladder sludge disappeared spontaneously within a relatively short time in 71.4% of patients, gallbladder sludge must be considered an important pathologic entity because gallbladder stones or complications such as acute cholecystitis occurred in 19.6% of patients. It remains for prospective studies to investigate whether therapy of gallbladder sludge may reduce the incidence of complications, particularly the development of gallstones and acute cholecystitis. We were not able to observe acute pancreatitis at least for the first year after sludge development.