The effects of enalaprilate on duodenal mucosal alkaline secretion (in situ titration) and mean arterial blood pressure were investigated in chloralose-anesthetized male rats. A bolus injection of enalaprilate (0.7 mg/kg intravenously) increased alkaline secretion by about 60%, and this response was resistant to guanethidine (5 mg/kg intravenously), splanchnicotomy, and vagotomy. Furthermore, angiotensin II infusion (0.25-2.5 microg/kg/hr intravenously) following the administration of enalaprilate failed to influence this response. Bradykinin (10(-6)-10(-4) M) applied topically to the serosal surface of the duodenal segment under study increased dose-dependently the duodenal mucosal alkaline secretion, an effect that could be blocked by the selective bradykinin receptor subtype-2 antagonist HOE140 (100 nmol/kg intravenously). HOE140 also antagonized the response to enalaprilate. These data suggest that enalaprilate increases duodenal mucosal alkaline secretion via a local bradykinin pathway involving receptors of the bradykinin receptor subtype-2 antagonist, rather than by blockade of endogenous angiotensin II or by central autonomic neural regulation.