Prior i.m. injection of pronethalol (10 mg./kg.), bilateral adrenalectomy, total destruction of the central nervous system, or bilateral denervation of the carotid sinuses reduced the duration of action of an i.v. injection of 10 mg. papaverine-HCl (I)/kg. against histamine bronchospasm in anesthetized guinea pigs.The time for 50% recovery of the response to histamine, after injection of I, was reduced from ∼55 min. to 14-22 min. by the above procedures.An i.v. injection of 10 mg. I/kg. into the anesthetized guinea pig decreased the blood pressure by 58 mm. Hg. and the time for 50% recovery was 16 min.Antagonism by I of histamine bronchospasm in anesthetized guinea pigs is mediated by 2 mechanisms; first, I acts directly on bronchial smooth muscles, and second, it acts by catechol amine release.