Obesity and weight loss are important risk factors for gallstone development. The mechanisms involved are unknown. We prospectively studied changes in gallbladder (GB) emptying and bile composition during weight loss. We studied 12 alithiasic obese subjects who entered a six-month diet program (800–1200 kcal/day, 26 g fat/day). As controls we evaluated 12 healthy nulliparous nonobese young women. GB volumes were studied by ultrasonography (fasting volume, GBFV; residual volume after a liquid meal, GBRV) at entry and after 4 and 20 weeks of dieting. Bile acid pool size, biliary lipid composition, presence of cholesterol crystals, and nucleation time were also studied. Of 12 obese subjects studied (mean BMI 35.1 kg/m²), 10 remained in the program for six months, but only six completed the entire study protocol, obtaining a significant weight loss (BMI: 31.2 kg/m², P < 0.001).="" gbfv="" was="" greater="" in="" obese="" subjects="" than="" in="" nonobese="" controls="" (27.5="" ±="" 10.7="" vs="" 11.7="" ±="" 6="" ml;="">P < 0.05).="" gbrv="" and="" gb="" emptying="" curves="" were="" similar="" in="" both="" groups="" and="" did="" not="" change="" during="" weight="" loss.="" the="" obese="" subject="" who="" developed="" gallstones="" (1/10)="" was="" the="" only="" one="" who="" had="" cholesterol="" crystals="" in="" bile="" and="" a="" sluggish="" initial="" gb="" emptying.="" in="" conclusion:="" (1)="" obese="" subjects="" had="" a="" greater="" gbfv="" than="" controls;="" however,="" the="" gb="" emptying="" was="" adequate.="" (2)="" during="" weight="" loss="" we="" did="" not="" observe="" significant="" changes="" in="" gb="" kinetics="" or="" the="" bile="" parameters="" studied.="" (3)="" we="" observed="" a="" relatively="" low="" frequency="" of="" gallstone="" formation,="" which="" can="" be="" explained="" by="" a="" high="" fat="" content="" of="" the="" diet="" (26="" g/day)="" and="" by="" the="" adequate="" gb="" emptying="" of="" our="" group="" of="" patients.="" (4)="" an="" abnormal="" gb="" contractility="" and="" cholesterol="" crystals="" in="" bile="" could="" be="" considered="" premonitory="" to="" gallstone="">