The relationship between polymorphisms in the interleukin-1 receptor antagonist (IL-1ra) gene and microbial vaginal colonization was examined in 88 asymptomatic women of reproductive age. Alleles of the intron 2 region of the IL-1ra gene were identified by polymerase chain reaction (PCR). PCR was also used to detect Ureaplasma urealyticum, Mycoplasma hominis, and Candida albicans; bacterial vaginosis (BV) was identified by clinical criteria. Among the 31 women with vaginal U. urealyticum, only 3 (9.7%) were homozygous for allele 2 of the IL-1ra gene; 21 (36.8%) of the 57 women who were negative for this organism were positive for allele 2 (P=.006). Only 7 women were positive for M. hominis; none were allele 2 homozygotes as opposed to 24 (29.6%) of the 81 women negative for M. hominis. There was no relation between C. albicans or BV and any IL-1ra allele. Reduced susceptibility to vaginal colonization with mycoplasmas may be associated with homozygosity of the 2 allele of the IL-1ra gene.