A 3-year prospective, blinded, multicenter study was done to assess the efficacy of early ribavirin intervention in mild respiratory syncytial virus illness in children with bronchopulmonary dysplasia or with congenital heart disease. A cohort of 178 children younger than 36 months of age with bronchopulmonary dysplasia or congenital heart disease were followed. Forty-seven infants whose respiratory syncytial virus infection resulted in mild symptoms of less than or equal to 72 hours' duration received ribavirin (n = 20) or water placebo aerosol (n = 27) either in a hospital or at home. Outcome measures included respiratory and analog score, room air oxygen, saturation, and oxygen flow needed to maintain saturation at greater than or equal to 91%. No difference in age, gender, family size, passive smoking, baseline oxygen saturations in room air, or duration of symptoms before treatment was found between groups. After 3 days of therapy, ribavirin produced a greater rate of improvement of analog scores (p = less than or equal to 0.001), lower oxygen requirements (p = 0.01), and higher oxygen saturation (p = 0.01). Respiratory scores and total hospital days did not differ significantly between the groups. Treatment failure occurred in 2 of 20 children (10%) in the ribavirin group versus 5 of 27 children (18%) in the placebo group, a nonsignificant difference. No child required assisted ventilation or had an adverse reaction. We conclude that early ribavirin therapy may help to reduce morbidity from respiratory syncytial virus infection in high-risk young children.