A high incidence of retinopathy of prematurity (ROP) was found in the very low-birth-weight infants discharged from the neonatal intensive care unit during the years 1977 to 1980, in spite of frequent monitoring of oxygen use. Although the yearly incidence of ROP in infants weighing less than 1,500 g varied between 35% to 36%, none were blind. The medical records of 65 infants with a birth weight between 501 and 1,250 g; surviving in 1979 to 1980, were reviewed in order to find risk factors for ROP. There were no significant differences between the 34 infants with ROP and the 31 infants who did not have ROP in mean birth weight or mean gestational age. Of 32 possible risk factors examined, the factors significantly associated with ROP were: apnea with mask and bag ventilation; prolonged parenteral nutrition; number of blood transfusions; and episodes of hypoxemia, hypercarbia, and hypocarbia. A highly significant association between hypocarbia and the development of severe ROP was found.