We studied prospectively a cohort of 326 neonates weighing 500-1250 gm at birth. These babies were all born at Magee-Womens Hospital during 1986 and 1987. Sixty-five percent survived and were discharged from the hospital, and 197 of the survivors (93%) had at least one ophthalmological exam before their discharge. Of the patients who were examined, 34% had retinopathy of prematurity (ROP) and 12% had stage 3 or 4 ROP in at least one eye. There were six neonates with at least one blind eye, giving an estimated prevalence of blindness caused by ROP of 301 per million live births. By univariate analysis there was a strong association of ROP with birthweight, oxygen exposure, respirator treatment, and intraventricular hemorrhage (IVH). By multivariate analysis, only the respirator treatment was significantly associated with ROP. When birthweight, oxygen exposure, and IVH were controlled, a baby requiring more than 28 days of ventilator treatment was 4.07 times more likely to have stage 3 or 4 ROP than a baby with less ventilator exposure. These data confirm the strong association of ROP with bronchopulmonary dysplasia (BPD), low birth-weight, and IVH, and suggest that the key component among these interrelated variables may be time spent on a ventilator.