Diminished gallbladder emptying has been implicated in the pathogenesis of gallstone formation. This study assessed the effect of the physical presence of inert, prosthetic gallstones on gallbladder contractility, histopathology, and bile composition. Three glass beads, each 3 mm in diameter, were implanted in the guinea pig gallbladder. Six weeks later the in vitro contractility was assessed in response to cholecystokinin. Sham-operated animals underwent cholecystotomy without bead implantation. The gross and microscopic appearance of gallbladders from sham-operated and implanted animals was the same. The presence of stones moderately inhibited gallbladder contraction reaching 20.5% (P less than 0.05) at the maximally effective dose of cholecystokinin compared to sham-operated animals. Sham-operated and control (unoperated) animals had similar gallbladder contractility. Thus surgery itself did not alter gallbladder motility. The presence of stones had no effect on biliary lipid composition. It thus appears that gallstones, in the unobstructed gallbladder, cause only a moderate inhibition of gallbladder contractility and have little effect on biliary physiology.