The mechanism of the inhibition of proximal duodenal motor activity by carbachol-induced antral contractions or by field stimulation was studied in anesthetized dogs that had strain gauges sutured 5 and 10 cm from the pylorus on the antrum and duodenum. The duodenum was excited by vagal stimulation or distal duodenal field stimulation. Duodenal inhibition was studied 1) during a control period and after the pylorus was transected followed by administration of phentolamine, 2) during control and after phentolamine followed by pyloric transection, 3) during control and after prazosin followed by yohimbine, and 4) during control and after yohimbine. Duodenal inhibition was greater when the antral stimulation or duodenal contractions were near the pylorus. Pyloric transection did not significantly reduce this inhibition; phentolamine then abolished it. Prazosin did not abolish inhibition but yohimbine did. In conclusion, antroduodenal inhibition under our experimental conditions was mediated primarily by sympathetic nerves modulating the activity of duodenal cholinergic nerves, which possess alpha 2-adrenoceptors, and to a less extent by intrinsic nerves crossing the pylorus.