To clarify the relationship between chorioamnionitis and chronic lung disease (CLD) in very low birth weight (VLBW) infants, we performed a retrospective cohort study of all inborn patients between 1995-1997 with gestational age (GA) less than 32 wk, birth weight less than 1.5 kg, survival to 36 wk adjusted GA, and placentas submitted to pathology (n = 371). Racial distribution as defined by the mother was 40% white/60% nonwhite. Prevalence of CLD, defined as O(2) dependence at 36 wk adjusted GA, was 30%. In a preliminary analysis GA and birth weight for GA (standard deviations from the mean, Z-score), considered together, were inversely related to CLD. After adjustment for GA and Z-score, other risk factors for CLD were white race, acute respiratory distress, pulmonary air leak, patent ductus arteriosus, and septicemia. Two placental lesions were inversely related to CLD: histologic chorioamnionitis and acute atherosis (a placental indicator of preeclampsia). Following multivariate analysis, independent risk factors for CLD were GA (OR, 0.6; 95% CI = 0.5, 0.7), birthweight for GA (OR, 0.4; 95% CI = 0.3, 0.6), white race (OR, 1.9; 95% CI = 1.0, 3.3), patent ductus arteriosus (OR, 2.0; 95% CI = 1.0, 3.5), and pulmonary air leak (OR, 3.0; 95% CI = 1.3, 7.1). Acute atherosis was inversely related to CLD (OR, 0.2; 95% CI = 0.1, 0.8). Chorioamnionitis was stratified by subtype and again no association with CLD was seen in the population as a whole. Finally, chorioamnionitis of all subtypes tended to be increased in white infants and decreased in black infants with CLD. This dichotomy was not explained by differences in death rates, acute respiratory distress, intubation on d 2 of life, or total duration of assisted ventilation. We conclude that while chorioamnionitis was not a risk factor for CLD in our total population, racial differences in its relationship to CLD are worthy of further study.