Chronic lung disease (CLD) is a common outcome of neonatal intensive care. To determine whether the results of serial exhaled nitric oxide (eNO) measurements during the perinatal period differed between infants who did and did not develop CLD. In addition, we wished to assess whether eNO results were more predictive of CLD development than lung function test results or readily available clinical data (gestational age and birthweight). The patients were 24 infants with a median gestational age of 27 (range 25-31) weeks. Measurements of eNO levels, functional residual capacity (FRC), and compliance of the respiratory system (CRS) were attempted on postnatal days 1, 3, 5, 7, 14, and 28 days. The 12 infants who developed CLD were of significantly lower birthweight and gestational age than the rest of the cohort; in addition, they had lower median FRC (P<0.02) and CRS (P<0.02) results, but not higher eNO levels, in the first week after birth. Construction of receiver operator characteristic (ROC) curves demonstrated that the CRS and FRC results on Day 3 were the best predictors of CLD development; the areas under the ROC curves were 0.94 and 0.91, respectively. Early lung function test results, but not eNO levels, are useful in predicting CLD development, but are not significantly better than birthweight.