Vaginal mucosa has been shown to play an important role in fertility, since several changes during the estrous cycle determine fertility and pregnancy outcome. The contribution of vaginal fluid IgG antibodies (Abs) to these changes is not fully characterized. Asymmetric Abs (AAb) are a subpopulation of IgG Abs bearing a carbohydrate residue in only one Fab region of the molecule, being therefore functionally univalent and unable to trigger immunological mechanisms tending to destroy the antigens. Here, we investigated the presence of AAb in vaginal secretions of virgin mice. Vaginal fluids were extracted from CBA/J female, where asymmetric IgG molecules were characterized by differential ELISA tests. Additionally, the phenotype of vaginal lymphocytes (VL) was analyzed by flow cytometry. Our data indicate a variation in the percentage of AAb during estrous cycle, since we observed a significant increase in asymmetric IgG molecules levels after ovulation. Regarding the AAbs isotypes, we identified IgG1 as the principal component of the synthesized AAbs. Eighty percent of the AAbs were directed against normal flora, and about 20% of them reacted with vaginal epithelium antigens. Flow cytometry studies revealed TCRalphabeta and gammadelta populations, but a lack of CD8+ T-cells in vaginal mucosa. Since we found a high concentration of AAbs in murine vaginal secretions during metestrus and AAbs were previously found to be protective, it is tempting to speculate that AAbs would provide protection of normal flora in the vaginal lumen. Additionally, we observed that the levels of AAbs decrease when susceptibility to infection in mice occurs at proestrus/estrus, further suggesting a protective role for AAbs.