The effects of 2 mg/kg/day theophylline (serum concentrations, 2.9 to 4.7 micrograms/ml) on metabolic rate were observed in 11 premature infants with severe idiopathic apnea of prematurity. Oxygen consumption (VO2/kg) increased 25% from 6.5 +/- 0.4 (SEM) to 8.1 +/- 0.6 cc/min/kg after 24 to 48 hr of therapy. Respiratory quotient did not change. Apnea and bradycardia decreased from 8.6 +/- 1.4 to 1.6 +/- 0.5 episodes/hr and 4.4 +/- 1.1 to 1.2 +/- 0.4 episodes/hr, respectively. This dose of theophylline is effective in idiopathic apnea of prematurity and acts as a metabolic stimulant. In the premature infant, theophylline-induced increases in VO2 may be a result of changes in the sleep state.