We compared previously healthy prematurely born infants with full-term infants hospitalized with respiratory syncytial virus (RSV) infection to evaluate the role of prematurity on the clinical course of the illness. During a 5-yr period (1984 to 1989), 484 previously healthy patients were admitted to the hospital with RSV infection. No differences were found in the presenting symptoms of respiratory distress, cough, fever or shock, although the premature group was more likely to present with apnea (p less than .001). Chest roentgenograms revealed that premature infants had a higher incidence of atelectasis/infiltrate and hyperinflation (p less than .05). Premature infants had longer hospital stays as well as a higher Physiologic Stability Index and Therapeutic Intervention Score (p less than .001). They were also more likely to receive supplemental oxygen, ICU admission, mechanical ventilation, and nothing by mouth status (p less than .001). We conclude that premature birth increases the risk of more severe and prolonged RSV disease.