OBJECTIVE: We examined the association between preterm delivery and polymorphisms at position +3953 of the interleukin-1 beta gene (IL1B+3953) and in intron 2 of the interleukin-1 receptor antagonist gene (IL1RN). STUDY DESIGN: This was a case-control study that involved 52 pregnancies that resulted in spontaneous preterm delivery before 34 weeks of gestation and 197 pregnancies that resulted in birth at term. Polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Homozygous carriage of IL1B+3953 allele 1 by fetuses of African descent was associated with a risk of preterm delivery (P =.033). Fetuses of Hispanic descent that carried IL1RN allele 2 were found to be at an increased risk for preterm premature rupture of membranes and subsequent preterm delivery(P =.021; odds ratio, 6.5; 95% CI, 1.25-37.7). CONCLUSION: There are associations of spontaneous preterm delivery with the fetal carriage of IL1B+3953*1 and IL1RN*2 alleles in African and Hispanic populations, respectively.