Respiratory distress syndrome of the newborn, prematurity, and familial airway hyperreactivity may contribute to long-term pulmonary sequelae. We assessed the role of each by testing pulmonary function and airway reactivity in 11 prematurely born children who survived the respiratory distress syndrome and in 11 prematurely born children who had no neonatal respiratory disease, each of whom was paired with a sibling born at term. The subjects were between 7 and 12 years of age when studied. Airway reactivity was also assessed in their mothers. The group who had had the respiratory distress syndrome had higher ratios of residual volume to total lung capacity and lower values for forced expiratory volume in one second than did their siblings or normal controls (P less than 0.01). Expiratory flow was decreased in both groups born prematurely (P less than 0.02) and was related to neonatal exposure to oxygen (r = -0.71, P less than 0.02). The incidence of airway hyperreactivity was elevated in all groups, including the mothers. These data suggest that long-term pulmonary sequelae of the respiratory distress syndrome of the newborn are related to the disease, its treatment, or both, and to airway hyperreactivity. In prematurely born children without neonatal lung disease, the sequelae are related to airway hyperreactivity. The possibility of a relation between familial airway hyperreactivity and premature birth is suggested.