This study was undertaken to determine in healthy humans the effect of graded physiologic doses of cholecystokinin (CCK) on gallbladder size as assessed by ultrasonography and to analyze the relations between the doses of CCK infused, the plasma CCK increments, the decreases in gallbladder volume, and the cumulative intraduodenal bilirubin output. Infusion of stepwise-increasing doses of CCK, ranging from 0.2 to 6.4 pmol/kg X h, induced dose-related increases in plasma CCK (r = 0.99; p less than 0.001), decreases in gallbladder volume (r = 0.99; p less than 0.001), and increases in intraduodenal bilirubin output (r = 0.96; p less than 0.01). There was a highly significant correlation between the decreases in gallbladder volume and the cumulative intraduodenal bilirubin outputs (r = 0.98; p less than 0.001). Infusion of 0.8 pmol/kg X h of CCK, resulting in an increase in plasma CCK of 1.3 +/- 0.5 pmol/L, was the threshold for stimulating gallbladder contraction as assessed by both ultrasonography and measurement of intraduodenal bilirubin output. It is concluded that ultrasonography is a sensitive method for the quantitation of gallbladder contraction and that physiologic plasma CCK concentrations do stimulate gallbladder contraction.