The effectiveness of aminophylline in the treatment of apnea of prematurity was evaluated in 13 premature infants (mean birthweight, 1.13 kg; mean gestational age, 29 weeks). Apnea was recorded by direct observation in combination with impedance monitoring. Rectal suppositories of aminophylline (5 mg) were given at six-hour intervals. The average dose was 4.1 mg/kg. No toxicity or complications were noted. The parents became free of apneic episodes during therapy. The response for each eight-hour interval of treatment over 72 hours when compared to pretreatment was significant (P less than .01; paired t-test), after the first eight hours. Only one patient required mechanical ventilation for apnea. Treatment was continued for 2 to 14 days (mean, 5 days). A recurrence of apnea was noted in nine patients after discontinuing aminophylline. All patients except one survived. No change in Po2, Pco2, pH, mean heart and respiratory rates, and blood pressure was noted. A direct effect on the respiratory center is postulated.