The purpose of these studies was to determine quantitatively the reflex cardiovascular responses to stimulation of the pulmonary C-fibers in dogs. We used a preparation in which the airway, pulmonary artery, and the pulmonary veins to the left lung were cannulated in situ. Ventilation and perfusion of the right lung maintained the animal in relatively normal homeostasis. Capsaicin, a decylenic acid amide of vanillylamine that selectively stimulates nerve endings of unmyelinated fibers (C-fibers), was injected into the left pulmonary artery in 5-ml boluses. Maximal reflex responses were obtained with concentrations as low as 0.8-1.6 X micrograms-1 X kg-1. Heart rate, hindlimb resistance, and left ventricular contractility were lowered transiently (the maximal responses showing declines of 40, 13, and 15.2%, respectively). As a result of these changes, combined with vasodilation in other resistance vessels, cardiac output fell 28% and blood pressure fell 35%. Interrupting the afferent neural pathway by severing the ipsilateral cervical vagus nerve eliminated these responses, confirming the distribution of their reflex origin. Although the role of these reflexes in homeostasis has not been decided, the results of this study suggest that the lungs of dogs, if appropriately stimulated, potentially can exert a major inhibitory influence on the neural regulation of cardiovascular function.