Our objectives were to determine whether the use of inhaled nitric oxide (iNO) for severe persistent pulmonary hypertension of the newborn (PPHN) causes impaired lung function during infancy. We therefore performed a prospective study of lung function in 22 infants after neonatal intensive care unit (NICU) discharge who had been treated for severe persistent pulmonary hypertension of the newborn (PPHN) with (n = 15) or without (n = 7) iNO, and compared these findings in lung function to those of healthy control infants (n = 18). Five infants with interstitial lung disease (ILD) were included to assure that the pulmonary function tests (PFT) were sensitive enough to detect abnormalities of lung function in this age group. We measured passive respiratory mechanics and functional residual capacity (FRC) using a commercially available system. All data were expressed as means and standard deviation. Statistical analysis was performed by analysis of variance (ANOVA). A Bonferroni multiple comparisons test was used for variables that showed overall group differences. Twenty-two infants were studied during follow-up 4-12 months after NICU discharge. None of the infants were actuely ill, and only one infant was on 0.25 L of oxygen per minute at the time of study. We found no differences in lung function between the treatment groups (iNO + mechanical ventilation (MV), or MV alone), or between either treatment group and healthy control infants of the same age. We were able to detect significant differences in functional residual capacity adjusted for weight or height, and compliance of the respiratory system adjusted for weight or lung volume in the ILD infants compared to the healthy controls or infants who had PPHN, indicating that these PFTs were sensitive enough to determine abnormal lung function in this age group. We conclude that inhaled nitric oxide therapy for the treatment of severe PPHN does not alter lung function as determined by lung volume and passive respiratory mechanics measurements during early infancy.