To investigate the association between a tumor necrosis factor-α (TNF-α) gene polymorphism, vaginal TNF-α level, and microbial flora in pregnant women.Vaginal samples from 203 women at 18–22 weeks’ gestation were analyzed for microflora. TNFA-308G>A polymorphism was analyzed by polymerase chain reaction and restriction endonuclease analysis and TNF-α concentration was determined by ELISA. Outcome data were subsequently obtained.The vaginal TNF-α concentration was elevated in TNFA-308A carriers only in the presence of abnormal vaginal flora. A median TNF-α level of 10.94pg/ml in TNFA-308A carriers with bacterial vaginosis (BV) was significantly higher than that of 1.77pg/ml in TNFA-308A carriers without BV (P=.02), and 1.72pg/ml in TNF-308G homozygotes with BV (P=.01).The TNFA-308G>A polymorphism influences the local TNF-α response to altered vaginal microflora. This suggests that the nature of the host response to microbial invasion in the lower female genital is genetically determined.