The role of muscarinic receptors in sympathetic ganglionic impulse transmission has not been clearly recognized in whole animal studies. However, in certain situations, the muscarinic receptors may participate in modulating blood pressure, and there is thus some evidence for their role in ganglionic transmission. Pirenzepine, a muscarinic receptor antagonist, elicited no significant changes in renal nerve activity (RNA) and blood pressure (BP) in normal rabbits; however, chlorisondamine, a ganglionic nicotinic receptor antagonist, caused marked decreases in RNA and BP in normal rabbits, reaching the nadir in 2 to 3 min and gradually recovering thereafter. In the presence of chlorisondamine, pirenzepine decreased both RNA and BP, but the recovery of chlorisondamine-induced decreases of both RNA and BP was attenuated by pirenzepine. McN-A-343, a muscarinic receptor agonist, caused a transient hypotensive effect. In the presence of chlorisondamine, McN-A-343 increased both RNA and BP in dose-related fashion, and the dose-response curves of McN-A-343 shifted to the right in the presence of pirenzepine. These results suggest that in sympathetic ganglia blockade of ganglionic nicotinic receptors activates muscarinic receptors which participate in regulation of peripheral sympathetic nerve activity and of blood pressure.