Identification of chemical markers in human embryo culture media that relate to embryo quality and implantation potential could be an invaluable tool in embryo selection for transfer. Embryonic secretion of soluble human leukocyte antigen G (sHLA-G) has been postulated to be a marker for 'embryonic competence'. This study examines sHLA-G concentrations in day 3 culture media droplets of embryos that were selected for transfer, as well as those being cryopreserved. A total of 712 embryo culture supernatants from 83 patients were assayed. Soluble HLA-G was detected in 306 of the 712 samples tested. In the 58 transfers in which at least one embryo selected for embryo transfer was positive for sHLA-G, the pregnancy rate was 64% (37/58) and the implantation rate per embryo transferred was 38%. In contrast, patients receiving only embryos that were negative for sHLA-G had both a lower pregnancy rate of 36% (9/25; P < 0.05) and a decreased implantation rate (19%; P < 0.05). Expression of sHLA-G was also related to increasing cell stage. Concentration of sHLA-G in embryo culture media was variable and in the low range (3-10 ng/ml). These data suggest an association between implantation potential and embryonic secretion of sHLA-G. The commercial assay kit utilized allowed for same day assessment of sHLA-G secretion. Addition of sHLA-G status to traditional morphological criteria may be useful as a clinical tool for embryo selection.