Thyrotropin-releasing hormone (TRH) was unable to induce any noticeable contraction of canine isolated gallbladder strips up to the dose of 10(-4) g/ml, while caerulein (CAER) was spasmogenic in a dose-related manner beyond 10(-11) g/ml. This effect of CAER was unaffected by either atropine or tetrodotoxin. In conscious dogs, the intravenous bolus of TRH (20 micrograms/kg) or CAER (0.2-2.0 micrograms/kg) caused gallbladder emptying. The TRH response, unlike that of an equipotent dose of CAER, was prevented by atropine. In experiments on electrical activity of the digestive tract in conscious dogs, both TRH or CAER induced a concomitant increase on the myoelectrical activity in the proximal part of the small intestine. The excitatory effects were prevented by atropine only in the case of TRH. These results demonstrate that TRH stimulates indirectly the gallbladder and proximal duodenum of the dog. They suggest the involvement of a cholinergic pathway in this excitatory action.