The effect of artificial ventilation on duodenal alkaline secretion and blood flow was studied in sodium pentobarbital-anaesthetized rabbits. A duodenal segment (approximately 3 cm) was cannulated in situ and continuously perfused with isotonic saline, and the bicarbonate secretion was titrated by pH-stat. Compared with the spontaneous breathing state, artificial ventilation improved the respiratory status of the animal, increasing Po2 and decreasing both Pco2 and plasma bicarbonate. Duodenal blood flow as measured with laser-Doppler flowmetry was not altered but the alkaline secretion was reduced. Pretreatment with the alpha 2-adrenoceptor antagonist yohimbine (0.5 mg kg-1 i.v., followed by 0.5 mg kg-1 h-1 i.v.) or the ganglionic blocker hexamethonium (10 mg kg-1 i.v.) did not affect the decline in duodenal alkaline secretion in response to artificial ventilation. Nor did these pretreatments affect the changes in plasma bicarbonate and Pco2 or significantly alter the blood flow. Increasing Pco2 in the respirator air increased the plasma Pco2 and bicarbonate concentration as well as the duodenal bicarbonate secretion. Pretreatment with the carbonic anhydrase inhibitor acetazolamide (80 mg kg-1 i.v.) reduced the bicarbonate secretion, and artificial ventilation induced a further reduction. Increasing Pco2 in the respirator in the animals pretreated with acetazolamide did not affect the bicarbonate secretion. Duodenal alkaline secretion was thus always reduced on artificial ventilation. The mechanism for this reduction does not seem to involve the sympathetic nervous system or the blood flow, but appears to be the consequence of alterations in the plasma concentration of bicarbonate and the plasma Pco2.