Rhesus monkeys were used to characterize the respiratory response (RR) to aerosolized physostigmine (Phy) and compare the response to the acute, reagin-mediated RR and the carbachol response. In the latter two responses, there are characteristic increases in frequency of respiration (f), pulmonary resistance (PR), and decreases in peak expiratory flow rate (PEFR), tidal volume (TV), and dynamic compliance (C). In contrast, a Phy RR characteristically shows no change in TV and f. The Phy RR is inhibited by atropine and lidocaine. The carbachol RR is inhibited by atropine but not lidocaine. The Phy RR mimics a vagally induced RR more closely than carbachol because it is inhibited by pharmacologic and physiologic vagal blockade produced by atropine and lidocaine, respectively, whereas the carbachol RR is blocked by atropine but not lidocaine. The carbachol block by atropine is primarily not a block of vagal action, but a general pharmacologic block of cholinergic action. The reagin-mediated RR is not inhibited by pharmacologic or physiologic vagal blockade. We conclude that a Phy-induced vagomimetic RR differs from a reagin-mediated, immediate-type RR. Although a minor portion, at most, of a reagin-mediated, immediate-type RR may be mediated via the vagus nerve, the major portion of a reagin-mediated RR occurs independent of the influences of the parasympathetic innervation of the lung.