Theophylline is commonly used to treat apnea of prematurity. To determine the effectiveness of theophylline with respect to gestational and postnatal age, we conducted a controlled study in 43 premature infants with idiopathic apnea. Three of the 21 treated and eight of the 22 control infants developed respiratory failure. Eight of the 11 infants with respiratory failure had gestational ages of less than 31 weeks and had more than four apneic episodes during the first day of life. In the treated infants without respiratory failure, the number of apneic episodes by 24-hour intervals declined six days earlier than in the control infants. Apnea disappeared, however, at a similar time in both groups. Three treated infants and three control infants had apneic episodes persisting beyond the neonatal period. Patients treated with theophylline did not develop respiratory failure as often as control infants did. However, despite a reduction of apneic episodes, theophylline did not shorten the course of apnea of prematurity.