Postprandial gallbladder contraction is mainly regulated by cholecystokinin (CCK), but little is known about the dose-response relationship between CCK release and gallbladder contraction, in particular after meals with differing fat content. Decreased postprandial gallbladder emptying has been suggested to play a major role in the development of gallstones in man, and dietary factors may therefore be important in the pathogenesis of gallbladder stasis. We studied, in a randomized order, the effect of three isocaloric meals (250 mi) with identical osmolality on CCK release and gallbladder contraction in six healthy volunteers: (1) a pure fat meal (25 g triglycerides); (2) a mixed meal containing fat (8 g, 29% of caloric content), protein (10 g, 17%), and dextrose (32 g, 54%); and (3) a fat-free meal containing albumin (25 g, 46%) and dextrose (32 g, 54%). Gallbladder volumes and antral cross-sectional areas were determined. by ultrasonography and plasma CCK and PP levels by RIA. The pure fat meal caused the highest CCK release (187 +/- 27; mean +/- SEM) and maximal (>85% of fasting volume) gallbladder contraction (3172 +/- 361; AUG) as compared to the other two meals (P < 0.05). The mixed and the fat-free meal caused similarly low (<50% of fasting volume) gallbladder contraction (6052 +/- 342 and 6134 +/- 500, respectively), although they induced markedly different CCK levels (157 +/- 12 and 87 +/- 13, respectively; P < 0.05). Gastric emptying rates were similar for all meals (18,500 +/- 3300, 18,600 +/- 2700 and 19,800 +/- 3100, respectively). The results of this study suggest that CCK plays a major role in the stimulation of gallbladder contraction but that other factors besides CCK are implied when fat-free or low-fat meals are ingested. Furthermore, our findings suggest that a fat intake of 25 g induces maximal gallbladder contraction and may thus prevent an understimulation of gallbladder contraction and the formation of gallbladder stones.