Several data suggest that muscarinic M-1 receptors are located on airway smooth muscle of human beings and dogs. Muscarinic M-1 receptors, whose stimulation is associated with enhancement of acetylcholine release, may also be located in the airway parasympathetic ganglia. To determine if postsynaptic muscarinic M-1 receptors mediate airway constriction, the action was compared of pirenzepine, that antagonizes selectively muscarinic M-1 receptors, and atropine, that blocks both muscarinic M-1 and M-2 receptors, on bronchial responses to methacholine inhalation in seven asthmatic patients. Pirenzepine and atropine gave protection against methacholine; however, the degree of protection by pirenzepine was significantly less than that given by atropine. Some inhibitory effect was obtained in all the patients studied after pirenzepine administration, even though some patients were only slight responders. The significant finding of the study is that pirenzepine partially inhibits the bronchospastic response to methacholine. This result suggests that muscarinic receptors on airway smooth muscle are also of the M-1 subtype.