To investigate whether nitric oxide (NO) is involved in surfactant-induced systemic and pulmonary vasodilatation in newborn piglets with surfactant deficiency, 2-6-d-old piglets were subjected to repeated saline lung lavages. They were then randomly assigned to one of two groups (seven in each group): theNω-nitro-L-arginine methyl ester (L-NAME) group received 3 mg/kg L-NAME i.v. 45 min before endotracheal instillation of 200 mg/kg porcine surfactant; the saline group received saline i.v. at the same time point, and instillation of 200 mg/kg surfactant. Mean arterial blood pressure, systemic vascular resistance, pulmonary arterial pressure, and pulmonary vascular resistance increased significantly after injection of L-NAME (allp< 0.01), whereas the cardiac index decreased significantly (p< 0.05). Saline injection did not change any variable. Significant decreases in mean arterial blood pressure (from a mean± SD of 66 ± 10 to 53 ± 9 mm Hg,p< 0.01), pulmonary arterial pressure (from 29 ± 6 to 23 ± 6 mm Hg,p< 0.01), and systemic vascular resistance (from 0.40 ± 0.13 to 0.33 ± 0.12 mm Hg/mL/min/kg,p< 0.05) were observed only in the saline group after surfactant instillation, whereas the decrease in pulmonary vascular resistance was not significant after surfactant instillation (p= 0.06). In contrast to the saline group, these variables were not modified in the L-NAME group after surfactant instillation. We conclude that the vasodilatory effect of porcine surfactant instillation in newborn piglets with surfactant deficiency is associated with activation of NO synthase.Abbreviations: a/A ratio,arterial/alveolar ratio of oxygen tension;CO,cardiac output;CVP,central venous pressure;Fio2, fraction of inspired oxygen;I:E ratio,ratio between inspiration and expiration times;L-NAME,Nω-nitro-L-arginine methyl ester;MABP,mean arterial blood pressure;NO,nitric oxide;Paco2, arterial tension of carbon dioxide;Pao2, arterial tension of oxygen;RDS,respiratory distress syndrome