The present study evaluated the incidence of gallstone formation in 105 morbidly obese patients undergoing rapid weight loss after proximal gastric bypass surgery. Intraoperative ultrasonography demonstrated gallstones in 20 (19%) and gallbladder sludge in four (4%) patients. Eighty-one patients had a normal gallbladder ultrasound. After bariatric surgery, these patients were followed prospectively with periodic gallbladder ultrasound examinations. At 6 months, gallstones had developed in 36% and gallbladder sludge in 13% of patients. These percentages remained relatively constant at 12 and 18 months. Body weight declined rapidly after surgery from a mean of 132.3 kg to 95.5, 87.0, and 84.0 kg at 6, 12, and 18 months, respectively. Gallstones developed significantly more often in the white race, and in women. No significant differences in age, body weight, percent ideal body weight, percent weight loss, or percent of excess body weight lost existed between patients who developed gallstones or sludge and those who did not. Patients who developed gallbladder sludge had less cholesterol and lower cholesterol saturation (1.25 +/- 0.42) in their gallbladder bile than persons who developed gallstones (2.00 +/- 0.79). Forty percent (13/32) of patients who developed gallstones became symptomatic; nine (28%) underwent elective cholecystectomy. An attempt to prevent gallstone formation during rapid weight loss appears warranted.