This study documents the effect of intravenous nitroglycerin (NTG) on tracheal smooth muscle in 12 patients undergoing coronary artery surgery. The pressure within a water-filled tracheal cuff was monitored continuously, as well as systemic and pulmonary arterial pressures. A significant decrease in cuff pressure after intravenous NTG (4.0 +/- 0.3 micrograms/kg) was detected before cardiopulmonary bypass (CPB). During CPB, with exclusion of the pulmonary arterial circulation, the tracheal cuff response to NTG administered into the oxygenator persisted and was not significantly different from that noted before CPB. Thus, the large airway (tracheal) response to NTG was independent of the pulmonary circulation and probably is mediated by the bronchial circulation. The response during CPB indicated that the tracheal smooth muscle retains tone and can respond to NTG even when the lungs are collapsed with no pulmonary arterial perfusion. These data were obtained from patients with no clinical evidence of reversible airway obstruction and indicate only that NTG relaxed human tracheal smooth muscle in vivo. These data do not demonstrate the efficacy of intravenous NTG in patients with asthma.