This study examined the risk factors for respiratory distress syndrome (RDS) in preterm infants from pregnancies complicated by placenta previa. Forty preterm infants born to mothers with placenta previa between January 1989 and December 1995 in a medical center were enrolled. Each of these patients was matched in gestational age and gender with an infant born immediately after to a mother without placenta previa. Obstetric and neonatal outcome variables were collected. The mean+/-S.D. gestational age for both groups was 33.0+/-3.1 weeks. There was no difference in mean birthweight between the placenta previa and control groups (2129+/-598 vs. 2136+/-493 g). All the patients in the former and 11 (28%) in the latter were born by cesarean section. About a half of the mothers in both groups received antenatal steroids. Infants from placenta previa pregnancies had a higher incidence (21/40 vs. 10/40, P<0.01) and more severe RDS than controls. Stratified by the status of treatment with antenatal steroid, we found that gestational age was a significant risk factor for RDS in both treated and untreated groups (P<0.01), but placenta previa was an independent risk factor (odds ratio 32; CI 1-4182) by multiple exact logistic regression in antenatal steroid-treated group. We conclude that preterm infants born to mothers with placenta previa had a higher risk for RDS than controls. It played an independent role, in addition to gestational age, only in infants treated with antenatal steroid. We speculate that placenta previa was not directly contributing to RDS, but through other associated risk factors for RDS.