In a thirty-month prospective study pleural effusions were found on chest radiographs in 33 of 1482 newborns admitted to intensive care units. Congenital heart disease was the most common cause, accounting for eleven cases. Meconium aspiration was the most common respiratory disease associated with neonatal pleural effusion. Infants whose effusions were first noted after the second day of life were likely to have heart disease (p = 0.02). Infants with moderate or large effusions were unlikely to have heart disease (p = 0.04). Prolonged pleural effusion was associated with a prolonged need for supplemental oxygen. Survivors whose effusions lasted three or more days were at increased risk for needing supplemental oxygen for more than twenty-one days (p = 0.07). The overall mortality was 48 percent (sixteen of thirty-three infants died).