Fetal inflammatory response has been previously shown to be involved in the pathogenesis of preterm premature rupture of membranes. We investigated the association between polymorphisms at position - 670 in the Fas gene and position - 124 in the Fas ligand gene demonstrated in neonatal oral mucosa cells and preterm premature rupture of membranes. Study design: Thirty-six singleton pregnancies were studied. Eighteen pregnancies were complicated by preterm premature rupture of membranes, and 18 were delivered at term without preterm premature rupture of membranes. Buccal swabs were obtained from each neonate, and extracted deoxyribonucleic acid was analyzed by polymerase chain reaction-based restriction fragment length polymorphism for an adenine (A) to guanine (G) substitution at position - 670 in the Fas promoter gene and at position- 124 in theFas ligand gene. χ 2 and Fisher’ s exact tests were used for statistical analysis. Results: There was no difference with respect to race, maternal age, and parity between the 2 groups. Frequencies of Fas - 670 AG, - AA, and - GG genotypes in preterm premature rupture of membranes group were significantly different from those in the control group (P = .004). The frequency of the heterozygous AG genotype was significantly higher in preterm premature rupture of membranes group as compared with controls (83.3% versus 33.3% , P = .003). Fas - 670 AA genotype was not observed among patients with preterm premature rupture of membranes. Similarly, the difference of frequencies of the Fas ligand - 124 AG, - AA, and - GG genotypes among preterm premature rupture of membranes group and controls was observed but did not reach statistical significance. Neither of the groups demonstrated homozygous GG genotype at position - 124 of the Fas ligand gene. Conclusion: Our data indicate an association between preterm premature rupture of membranes and increased prevalence of neonatal AG genotype at - 670 Fas promoter gene. Genetically predetermined regulation of the Fas/Fas ligand system appears to play an important role in the pathogenesis of the preterm premature rupture of membranes. We investigated the association between polymorphisms at position-670 in the Fas gene and position-124 in the Fas ligand gene demonstrated in neonatal oral mucosa cells and Eighteen pregnancies were complicated by preterm rupture of membranes, and 18 were delivered at term without preterm rupture of membranes. Buccal swabs were obtained from each neonate, and extracted deoxyribonucleic acid was analyzed by polymerase chain reaction-based restriction fragment length polymorphism for an adenine (A) to guanine (G) substitution at position - 670 in the Fas promoter gene and at position- 124 in the Fas ligand gene. ’s exact tests were used for statistical analysis. Results: There was no difference with respect to race, mate Frequencies of Fas - 670 AG, - AA, and - GG genotypes in preterm premature rupture of membranes groups were significantly different from those in the control group (P = .004). The frequency of The heterozygous AG genotype was significantly higher in preterm premature rupture of the membranes group as compared with controls (83.3% versus 33.3%, P = .003). Fas - 670 AA genotype was not observed among patients with preterm premature rupture of membranes. Similarly, the difference of frequencies of the Fas ligand - 124 AG, - AA, and - GG genotypes among preterm premature rupture of membranes groups and controls was observed but did not reach statistical significance. Neither of the groups represented homozygous GG genotype at position - 124 of the Fas ligand gene. Conclusion: Our data indicate an association between preterm premature rupture of membranes and increased prevalence of neonatal AG genotype at - 670 Fas promoter gene. Genetically predeterm ined regulation of the Fas / Fas ligand system appears to play an important role in the pathogenesis of the preterm premature rupture of membranes.