204 infants with birthweights between 751 and 2000 g and 26-35 weeks gestational age (100 treated and 104 control subjects) were enrolled in a prospective controlled trial of the effectiveness of D-penicillamine (DPA) in the prevention of retinopathy of prematurity (ROP). The two groups did not differ significantly in gestational age, birth weight, Apgar scores, the time of exposure to oxygen and in the incidence of PDA or in the number of exchange transfusions and RBTs. Of the treated infants 29, and of the control infants 34 died before the tenth week of life. These cases were not included in further analysis. Patients were subsequently examined and assessed by two ophthalmologists independently, who did not know which babies were receiving DPA. Six of the 70 surviving control infants and none of the 71 surviving treated infants had ROP stage II or graver. The results suggested that ROP may effectively be prevented with DPA in very low-birth-weight-infants, and that the drug has no serious adverse effects during the neonatal period.