We studied the importance of exposure to an elevated partial pressure of carbon dioxide (PCO2) in the development of scarring retinopathy of prematurity (SROP) in a cohort of 92 neonates with chronic lung disease (greater than or equal to 14 days of respiratory therapy, greater than or equal to 30 days of oxygen therapy, and greater than or equal to 70 days in the hospital), 31 of whom had SROP. This cohort was chosen to avoid confounding prolonged respiratory failure with the presence of SROP and because such a cohort was expected to contain approximately 85% of all patients with SROP. Patients with SROP had a lower PCO2 and spent more time on a respirator at higher respirator pressures during the first 70 days of life. In addition, infants with SROP had a lower mean arterial pressure and had a higher prevalence of seizures (97% vs 43%) and intraventricular hemorrhage (52% vs 26%). We conclude that an elevated PCO2 is not associated with SROP in this group of critically ill premature neonates but that the presence of a seizure disorder or an intraventricular hemorrhage is strongly associated with SROP.