• During a 22-year period, 12 cases of spontaneous chylothorax in newborns were diagnosed at a large pediatric tertiary care center. Seven infants had right-sided effusions; only one effusion occurred on the left. Severe bilateral accumulations occurred in four nonimmune hydropic premature infants. The diagnosis was made by the milky appearance and/or the presence of more than 80% lymphocytes in the pleural fluid. Early diagnosis of the pleural effusion as chyle was associated with a less protracted course than when diagnosis was delayed. The total pleural fluid losses varied from 130 to 3,308 mL. Initial treatment included chest taps and/or drains in all the infants and mechanical ventilation in six. Oral feedings with standard or medium-chain triglyceride formulas were given in five; total parenteral nutrition was administered in seven. The conditions of two infants with copious and persistent drainage improved following surgery. All but one infant survived, and the chylothoraxes never recurred.