We investigated the development of gallstones over an 8-week period from the onset of dieting in 51 obese men and women and 26 nondieting control subjects. Gallbladder examinations were performed by abdominal real-time ultrasonography for the detection of gallstones. Initial sonography was performed prior to dieting and only those subjects in whom initial sonograms showed no gallstones or sludge were included in the study. Repeated sonography was performed at 4-week intervals for 8 weeks while they remained on a 2100-kJ/d diet. Initial weight of subjects prior to dieting averaged 105.9 +/- 3.8 kg (162% of ideal body weight) and decreased to 89.4 +/- 3.2 kg (137.3% of ideal body weight) after 8 weeks of dieting. Sonography performed after 4 weeks of dieting revealed new-onset gallbladder sludge in 1 subject and gallstones in 4 subjects. After 8 weeks of dieting sludge was detected in 3 subjects and gallstones in 13 (25.5%). In contrast, none of the nondieting subjects developed any detectable gallbladder abnormalities. During the dieting period, 1 of 51 subjects developed symptoms of biliary colic, necessitating cholecystectomy. On cessation of dieting with reinstitution of normal feeding, 2 additional subjects with stones developed symptoms severe enough to require cholecystectomy. In all 3 cases, cholesterol gallstones were recovered at the time of surgery. Eleven of the 13 patients with gallstones were followed up for 6 months after discontinuation of the diet. Besides the 3 undergoing cholecystectomy, 4 subjects had gallstones on follow-up ultrasound examination, while sonographically detectable gallstones had disappeared in 4 subjects. We conclude that this form of weight-reduction dieting predisposes to the development of gallstones and that gallstone formation is a risk of this type of prolonged calorie restriction. Dissolution or evacuation of gallstones may occur with resumption of a normal diet.