Antenatal administration of steroids (betamethasone 12 mg i.m. twice q 24 hr) enhances fetal lung maturation and reduces neonatal morbidity in preterm prelabor rupture of membranes (PROM). However, the risks of repeated administration of steroids 7 days after the initial course are unknown. We evaluated the prevalence of histologic evidence of chorioamnionitis in patients receiving single versus multiple courses of steroids for fetal lung maturation. We performed a retrospective analysis of consecutive cases of preterm PROM at < 32 weeks' gestation prospectively collected between July 1988 and March 1994. Obstetric and clinical information were obtained for women who did not receive steroids for fetal lung maturity (n = 55), those who received a single course (n = 47), and those with > or = 2 courses of steroids (n = 89). Placental pathology examination was performed after delivery, and histologic evidence of acute placental inflammation was determined and scored semiquantitatively on a scale of 0-4, as previously described. Potential confounding variables considered were: presence of oligohydramnios (vertical pocket of amniotic fluid < or = 1 cm at ultrasound), onset of labor prior to delivery, gestational age at delivery, and mode of delivery. The three groups were comparable for gestational age at membrane rupture and at delivery, rate of oligohydramnios, labor prior to delivery, and mode of delivery. Administration of multiple courses of steroids was associated with a decrease in the rate of clinical chorioamnionitis (p < 0.0001) and severity of histologic acute placental inflammation (mean +/- SD total score of acute inflammation: 10.7 +/- 7.2 vs. 7.3 +/- 6.0 vs. 6.9 +/- 6.0, p = 0.005) compared with the groups receiving no steroids or administration of a single course of steroids. In preterm PROM at < 32 weeks, repeated administration of courses of steroids is not associated with an increase in the prevalence of clinical or histologic evidence of infectious outcome. These findings may reflect a greater likelihood for noninfected patients to remain quiescent and thus receive repeated courses of steroids.