Continuous positive airway pressure (CPAP) administered as a mixture of oxygen and compressed air via nasal prongs has dramatically improved survival rates and lessened the frequency of barotrauma and bronchopulmonary dysplasia in the premature infant with respiratory distress syndrome. Associated with the increased use of nasal CPAP has been the development of marked bowel distension (CPAP belly syndrome), which occurs as the infant's respiratory status improves and the baby becomes more vigorous. To identify contributing factors, we prospectively compared 25 premature infants treated with nasal CPAP with 29 premature infants not treated with nasal CPAP. Infants were followed up for development of distension, defined clinically as bulging flanks, increased abdominal girth, and visibly dilated intestinal loops. We evaluated birth weight, weight at time of distension, method of feeding (oral, orogastric tube), and treatment with nasal CPAP and correlated these factors with radiologic findings. Of the infants who received nasal CPAP therapy, gaseous bowel distension developed in 83% (10/12) of infants weighing less than 1000 g, but in only 14% (2/14) of those weighing at least 1000 g. Only 10% (3/29) of infants not treated with nasal CPAP had distension, and all three weighed less than 1000 g. Presence of sepsis and method of feeding did not correlate with occurrence of distension. Neither necrotizing enterocolitis nor bowel obstruction developed in any of the patients with a diagnosis of CPAP belly syndrome. Our study shows that nasal CPAP, aerophagia, and immaturity of bowel motility in very small infants were the major contributors to the development of benign gaseous bowel distension.