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 wk). Apnea was recorded by direct observation in combination with impedance monitoring. Rectal suppositories of aminophylline (5 mg) were given at 6 h 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 8 h interval of treatment over 72 h when compared to pretreatment was significant (P < .01; paired t-test), after the first 8 h. Only 1 patient required mechanical ventilation for apnea. Treatment was continued for 2-14 days (mean, 5 days). A recurrence of apnea was noted in 9 patients after discontinuing aminophylline. All patients except one survived. No change in PO2 [O2 tension], PCO2 [CO2 tension], pH, mean heart and respiratory rates and blood pressure was noted. A direct effect on the respiratory center is postulated.