The efficacy of caffeine citrate in the management of apnea in the newborn infant was evaluated. Caffeine citrate was given to 18 preterm neonates with recurrent apneic spells. Mean (+/- SE) birth weight and gestational age were 1,065.0 +/- 71.9 gm and 27.5 +/- 0.6 weeks, respectively. Mean age at onset of apnea and at initiation of caffeine treatment was 6.5 +/- 3.7 days and 18.2 +/- 4.9 days, respectively. Caffeine citrate was administered with a loading dose of 20 mg/kg intravenously followed within two to three days by 5 to 10 mg/kg once or twice daily. All infants except one showed a significant decrease in the frequency of apneic episodes associated with caffeine therapy. Mean frequencies of apneic spells were 13.6 +/- 2.5 and 2.1 +/- 0.6 apnea per day before and after initiation of caffeine treatment, respectively. Respiratory rate was increased, and blood [h]+ion concentration and Pco2 were decreased. The data suggest that caffeine is an effective pharmacologic respirogenic agent in the preterm infant with apnea.