To determine the relative role of nicotinic and muscarinic mechanisms in splanchnic nerve stimulation (NS)-induced adrenal catecholamine secretion and medullary vasodilation, 12 pentobarbital-anesthetized dogs were subjected to three identical stimulations. The first NS was performed before drug administration and served as a control. The second NS was performed after administration of either the muscarinic antagonist, atropine 0.5 mg/kg (group 1), or the nicotinic antagonist, hexamethonium 20 mg/kg (group 2). The third NS was performed after administration of both drugs. NS in the absence of drug resulted in 4-fold and greater than 200-fold increases in medullary blood flow (Q, measured with radiolabeled microspheres) and catecholamine secretion (assayed by high-pressure liquid chromatography), respectively. Atropine, when administered alone (group 1), had no effect on these responses. Subsequent administration of hexamethonium to group 1 animals resulted in complete blockade of NS-induced changes in medullary Q and secretion. Hexamethonium alone (group 2) reduced the catecholamine response to NS by 95% but had no effect on the medullary Q response. Addition of atropine further attenuated the increase in catecholamine secretion induced by NS and completely blocked the medullary Q increase. These data suggest the presence of redundant mechanisms to increase medullary Q during NS. One mechanism likely involves neurally released acetylcholine-stimulating vascular muscarinic receptors, whereas the second requires either chromaffin cell degranulation or nicotinic ganglionic transmission.