Intravenous infusion of motilin (0.3-0.9 micrograms/kg-hr) during the interdigestive state induced a transient but strong tonic contraction in the gallbladder, which was similar to the natural interdigestive gallbladder contraction, as well as a typical IMC in the stomach and the duodenum. This motilin-induced contraction always occurred simultaneously with the intitiation of phase II contractions of the IMC in the duodenum. The increase in contractile force (11.5 +/- 0.57 g) was not related to the dose of motilin tested. In contrast, intravenous infusion of CCK-octapeptide (CCK-OP, 0.03-0.09 micrograms/kg-hr) induced a dose related tonic contraction (7.8 +/- 0.41-17-7 +/- 0.77 g) which lasted as long as the CCK-OP infusion continued during the interdigestive state. Atropine sulfate (0.025 mg/kg) strongly inhibited both motilin- and CCK-OP induced gallbladder contractions. The present study indicates that the canine gallbladder in the conscious state is responsive to at least two hormonal factors, motilin and CCK. The contractile response of the gallbladder to motilin is quite different from the response to CCK-OP. However, both responses are mediated at least partially by cholinergic pathways.