Inhaled nitric oxide (NO) is known to selectively reduce pulmonary hypertension and improve the ventilation-perfusion relationship in subjects with lung injury of various origin. However, some forms of lung injury do not react to inhaled NO at all, or show only a reduction in pulmonary arterial pressure. Very little is known about the effects of inhaled NO after smoke inhalation injury. We investigated the effects of inhaled NO in an established model of ovine smoke inhalation injury. Chronically instrumented sheep («=8) had tracheostomies and were insufflated with smoke generated from burning cotton cloth (4 times at 12 breaths each). They were then connected to a ventilator with oxygenenriched air to achieve arterial oxygen tensions within the normal range. After 48 hours, NO was added to the inspired gas in ascending concentrations of up to 100 ppm. Systemic and pulmonary hemodynamics as well as oxygen transport were analyzed. Inhaled NO dose dependently lowered the pulmonary hypertension. Concentrations higher than 20 ppm did not further reduce the pulmonary artery pressure. Right ventricular stroke work index was significantly improved owing to die reduction in pulmonary vascular resistance. Arterial oxygenation, however, was not optimized by inhaled NO, probably because of interstitial edema formation.