To evaluate effects of cholinergic receptor stimulation on regional adrenal blood flow (Q, radiolabeled microspheres) and catecholamine secretion, acetylcholine (ACh) was infused into pentobarbital-anesthetized, ventilated dogs. Unilateral adrenal denervation and placement of lumboadrenal catheters preceded intra-aortic infusion of 1) ACh alone (n = 6), 2) ACh plus hexamethonium (Hex) 20 mg/kg (n = 6), or 3) ACh plus atropine (Atr) (0.5 mg/kg) and Hex. ACh alone and in combination with Hex elicited similar dose-related (2, 20, and 100 mumol/min) increases in catecholamine secretion (181 +/- 61 to 1,055 +/- 229, 31,644 +/- 9,411, and 179,181 +/- 69,659 ng.min-1 x g medulla-1), whereas Hex and Atr together inhibited ACh-induced secretion by 95%. ACh caused marked medullary vasodilation (0.71 +/- 0.05 to 0.14 +/- 0.03 mmHg.ml-1 x min.100 g) in all three groups. To determine whether medullary vasodilation was due to incomplete muscarinic blockade, Hex-pretreated animals (n = 4) received ACh (100 mumol/min) and three increasing doses of Atr (0.5, 5, and 25 mg/kg). Catecholamine secretion was inhibited by all doses of Atr; however, vasodilation was blocked only by the two higher doses of Atr. These data suggest possible different mechanisms of muscarinic receptor-mediated catecholamine secretion and vasodilation.