An adenovirus (Ad) type 8 outbreak was prospectively studied in a neonatal intensive care unit. Nasopharyngeal secretions were cultured weekly for viruses and clinical information was obtained daily in each infant. Eleven of 112 neonates were infected with Ad; 8 of 9 available isolates represented one variant of Ad 8. The median age at infection was 54 days and the median duration of virus shedding was 2 days. Seven of 11 infants had onset of new symptoms and/or required acute respiratory support; only 2 infants had eye disease. Maternal characteristics, race, gender, age at entry into study and respiratory distress syndrome at birth were similar for both groups. Ad-infected infants tended to have earlier gestations and lower birth weights. Ad-infected neonates stayed longer in the neonatal intensive care unit, required more days of respiratory support and were more likely to develop bronchopulmonary dysplasia. Thus an association was established between lung disease in premature neonates and Ad infection.