Currently, different approaches are used to select oocytes for in vitro fertilization (IVF) procedures, but they do not assure a significant association with the pregnancy outcome. Since several studies have proposed the expression of HLA-G antigens in early embryos to be a possible marker of elevated implantation rate, we have investigated the presence of soluble HLA-G molecules in 50 follicular fluids (FFs). The results have shown soluble HLA-G antigens (sHLA-G) in 19/50 (38%) FFs. Furthermore, we have related the presence of sHLA-G molecules in FFs to detection of the soluble antigens in culture supernatants of the corresponding fertilized oocyte, evidencing a significant relationship (p=1.3 x 10(-6); Fisher exact p-test). Specific ELISA and Western blot approaches identified both HLA-G5 and soluble HLA-G1 molecules in FFs while immunocytochemical analysis indicated polymorphonuclear-like and granulosa cells as responsible for production of sHLA-G1 and HLA-G5 molecules. In contrast, only sHLA-G1 antigens were detected in culture supernatants of fertilized oocytes. Overall, these results suggest a role for sHLA-G molecules in the ovulatory process and propose the FFs analysis for sHLA-G molecule presence as a useful tool for oocyte selection in IVF.