VIP, an endogenous neuropeptide normally present in lungs and other organs, relaxes isolated strips of human bronchus, pulmonary artery, and lung parenchyma in vitro. Pretreatment of these tissues with indomethacin (1 micrograms/ml) markedly enhances the basal tone and the relaxant effect of VIP. The VIP-induced relaxation, especially of pulmonary artery, has a long duration. As a relaxant of human pulmonary arterial strip, VIP is approximately 200 times as potent as prostacyclin, on a molar basis. The results suggest a possible role for VIP as a modulator of airway and pulmonary vascular tone, and as a potential bronchodilator and pulmonary vasodilator in human subjects.