To investigate whether bronchial C-fiber stimulation induced by capsaicin inhalation evokes nonadrenergic inhibitory (NAI) system bronchodilation, we studied partial and maximal expiratory flow-volume (PEFV and MEFV) curves in 5 normal subjects after inhalation of oxitropium bromide and propranolol. PGF2 alpha (1 mg/ml inhaled for 5 min) was administered to induce bronchoconstriction. Then aerosolized capsaicin was inhaled (2.4 x 10(-9) mol) to stimulate bronchial C-fibers. PGF2 alpha produced significant bronchoconstriction; FEV1 and flow during a PEFV curve at 30% forced vital capacity (V30p) decreased over a 15-min period. Capsaicin induced significant bronchodilation; V30p increased for 2 to 6 min (0.001 less than p less than 0.02), and FEV1 increased for 2 to 4 min (p less than 0.05) when compared with saline-ethanol (vehicle of capsaicin) inhalation. After treatment with the ganglionic blocking agent hexamethonium, the significant bronchodilator response disappeared. These results suggest that the NAI system has a distinct bronchodilator action in human subjects in vivo, and that the bronchial C-fiber receptors may be involved in the reflex pathway for NAI system bronchodilation in humans.