To study the pulmonary vasodilator selectivity of low levels of inhaled nitric oxide (NO) in a model of neonatal pulmonary hypertension, we sequentially exposed anesthetized, spontaneously breathing neonatal pigs to each of four different inspired gas mixtures: room air, room air with 25 parts per million NO, hypoxia (14% O2 in N2), and hypoxia with 25 parts per million NO. The room air, room air with NO, hypoxia, and hypoxia with NO exposures were of 15-min duration. The following measurements were made: mean systemic arterial, mean pulmonary arterial, and wedge pressures; thermodilution cardiac output; esophageal pressure; tracheal flow; and arterial Po2, Pco2, pH, hemoglobin, and methemoglobin. Inhalation of NO decreased pulmonary arterial pressure in both room air and hypoxia conditions (mean pulmonary arterial pressure 16 ± 1 torr room air, 13 ± 1 torr room air with NO, p < 0.005; and mean pulmonary arterial pressure 21 ± 2 torr hypoxia, 14 ± 1 torr hypoxia with NO, p < 0.005). NO had no significant effect on systemic arterial pressure, cardiac output, dynamic lung compliance, pulmonary resistance, or the measured blood variables during either control or hypoxic conditions. The results indicate that inhaled NO was a selective pulmonary vasodilator that could effectively reverse acute hypoxic pulmonary vasoconstriction. The normoxic vasodilation produced by NO inhalation also indicates the existence of basal vasomotor tone in the anesthetized, spontaneously breathing neonatal pig. The short-term exposures used produced no detectable manifestations of toxic side effects.