OBJECTIVE: We examined the effect of exposure to amniotic fluid infection and cytokines on the pulmonary outcome of preterm infants. STUDY DESIGN: A cohort of 136 preterm infants born to women in preterm labor had amniotic fluid cultures and tumor necrosis factor-α assays performed. Amniotic fluid was collected by transabdominal amniocentesis. Outcome measures included respiratory distress syndrome and length of oxygen and ventilator support. Logistic regression and Cox proportional hazards regression adjusted for birth weight and other confounders. RESULTS: Respiratory distress syndrome developed in 67 (49%) of 136 infants. Elevated amniotic fluid tumor necrosis factor-α levels and amniotic fluid infection were significantly associated with respiratory distress syndrome. This association persisted after adjustment for birth weight. Infants exposed to tumor necrosis factor-α remained on supplemental oxygen and assisted ventilation longer and had longer hospital stays compared with nonexposed infants. CONCLUSION: Prenatal exposure to tumor necrosis factor-α may be a risk factor for respiratory distress syndrome and its complications.(Am J Obstet Gynecol 1997;177:50-6.)