Hypovolemia inhibits duodenal mucosal alkaline (HCO-3) secretion by activation of sympathoadrenergic nerves. A possible involvement of the renin-angiotensin system was investigated. Experiments were performed on chloralose-anesthetized rats. The mucosal alkaline output by a duodenal segment was measured using in situ pH-stat titration equipment. A modest hypovolemia was induced by bleeding the animals approximately 10% of the total blood volume. This procedure decreased duodenal mucosal alkaline secretion to a sustained level of approximately 50% of baseline and reduced mean arterial pressure by approximately 20 mmHg. Intravenous pretreatment with the angiotensin-converting enzyme (ACE) inhibitor enalaprilate (0.7 mg/kg) or the angiotensin II-receptor antagonist losartan (10 mg/kg) altered the response to hypovolemia to a transient one, and alkaline secretion returned to the control level within 40-50 min. When exogenous angiotensin II was administered intravenously (0.25 and 0.75 microgram.kg-1.h-1), a hypovolemia-induced sustained depression of the secretion was observed even during ACE inhibition. Direct electrical stimulation (3 Hz, 5 V, 5 ms, bilaterally) of the peripheral splanchnic nerves decreased duodenal mucosal alkaline secretion to approximately 60% of the control level and increased mean arterial pressure by approximately 20 mmHg. However, in enalaprilate-pretreated animals, the inhibition of alkaline secretion due to splanchnic nerve stimulation was transient, a response that became sustained on angiotensin II substitution. These results suggest that the renin-angiotensin system prolongs the sympathoadrenergic inhibition of duodenal mucosal alkaline secretion and that angiotensin II, in this regard, acts mainly on the peripheral sympathetic efferents.