Ten preterm infants (birth weight 0.970 to 2.495 kg) with apnea due to periodic breathing (apneic interval = 5 to 10 seconds) or with "serious apnea" (greater than or equal to 20 seconds) were studied before and after the administration of theophylline. We determined the incidence of apnea, respiratory minute volume, alveolar gases, arterial gases and pH, "specific" compliance, functional residual capacity, and work of breathing. Theophylline decreased the incidence of apnea (P less than .05), increased respiratory minute volume (P less than 0.001), decreased (PACO2 (and PaCO2 P less than 0.001), increased the slope of the CO2 response curve (P less than 0.02) with a significant shift to the left (P less than 0.02). These findings suggest that the decreased incidence of apnea after theophylline is associated with an increase in alveolar ventilation and increased sensitivity to CO2 with a pronounced shift of the CO2 response curve to the left. These data are consistent with the idea that apnea is a reflection of a depressed respiratory system.