Objective: The objective of the study was to determine whether there are differences in the placental histology and various markers of infection/inflammation between preterm male and female fetuses. Study design: The placentas and umbilical cords of 446 infants born at 23 to 32 weeks were examined histologically, cultured for aerobic and anaerobic bacteria and mycoplasmas, and the interleukin-6 levels in cord blood determined. Results: Male infants were significantly more likely to have positive placental cultures than female infants (63.4% versus 51.8%, P = .01, odds ratio 1.5, 1.0 to 2.4). Cord blood Mycoplasma hominis and Ureaplasma urealyticum infections were marginally more common in male than female fetuses (27.6% versus 19.2%, P = .06, odds ratio 1.7, 0.9 to 2.9), but cord blood interleukin-6 levels were not different between male and female fetuses. The only significant histologic difference between male and female placentas was in decidual lymphoplasmacytic cell infiltration (6.3% versus 0.9%, P = .003, odds ratio 8.3, 1.8 to 39.0). Males had a higher percentage of decidual lymphohistiocytic cell infiltration, but the differences were not significant (11.3% versus 7.4%, P = .160, odds ratio 1.6, 0.8 to 3.2). Conclusion: Male infants were significantly more likely to have positive placental membrane cultures than female infants. Decidual lymphoplasmacytic cell infiltrations were more common in male versus female placentas, confirming a previous observation and suggesting that a maternal immune reaction to fetal tissue may be more common in male fetuses. © 2006 Mosby, Inc. All rights reserved.