The influence of somatostatin on the concentrating function and motility of the feline gallbladder has been studied with perfusion techniques in vivo. Somatostatin did not cause any change in the basal volume or concentrating function of the gallbladder. Duodenal acidification and also efferent electrical stimulation of the vagus nerves after atropinization reduced the net water absorption from the gallbladder, and these effects were blocked by intravenous somatostatin. The enhanced rate of net water absorption in response to electrical stimulation of the splanchnic nerves, however, was not influenced by somatostatin. Both the gastrointestinal peptides vasoactive intestinal peptide (VIP) and secretin reduce the net water absorption in the gallbladder. The blocking effect of the gallbladder's response to duodenal acid might be explained by an inhibition by somatostatin of secretin release from the duodenum. The inhibition of the gallbladder's reaction to vagal stimulation can be explained by a suppression of VIP release from noncholinergic, nonadrenergic nerve fibres in the gallbladder wall. Apart from the earlier described interference with gallbladder emptying, somatostatin seems to affect the regulation of the gallbladder's concentrating function. The results are discussed in view of the recent observation that patients with somatostatinoma characterized by high levels of circulating somatostatin usually have gallstone disease.