In anesthetized, spontaneously breathing rabbits, intratracheally administered isotonic saline, acetylcholine (Ach) and histamine (His) induced an increase of airway resistance up to 183, 571, and 312%, respectively, compared with untreated controls. This was accompanied by a decrease of the arterial pO2. Bilateral cervical vagotomy led to nearly complete inhibition of the saline- and Ach-induced bronchoconstriction, whereas the His effect was only reduced to 202%. Vagotomy did not improve the arterial pO2. While the bronchoconstrictive effects of isotonic saline and Ach revealed a significant linear correlation with the increased cGMP/cAMP ratio, His did not cause an alteration of the cGMP/ cAMP ratio to a degree that corresponds to its bronchoconstrictive activity. These data indicate that (1) bronchoconstriction-inducing agents may act (a) by stimulation of the parasympathetic nerve or (b) by contracting smooth muscles directly; (2) alveolar ventilation is not regulated by the parasympathetic nerve, and (3) bronchoconstriction induced by parasympathetic stimulation is associated with or mediated by an increase of the cGMP/ cAMP ratio