When there is a risk of inherited disease, preimplantation diagnosis gives couples an opportunity to avoid having a child with the disease. Sex determination can be used to exclude the likelihood of a sex-linked disorder. Accuracy of the diagnosis is important. We have tested the reliability of sex determination based on the recognition of a testis-determining gene (SRY) sequence. DNA from the blood of 120 men and women and from 38 single lymphocytes was amplified by polymerase chain reaction (PCR) with the SRY and control (ZP3) gene primers. All results confirmed the correct sex of origin (100%). The test was then used to determine the sex of 21 single embryo cells biopsied from 21 (4-8 cell) human polyspermic embryos. 2 embryo cells recognised at biopsy to have degenerated produced negative results. The other 19 single embryo cells showed 100% PCR amplification. 11 (58%) of the embryos were judged to be "male" and 8 (42%) "female". The SRY and ZP3 gene primers selected are highly specific and give accurate results in sex determination and their use provides a new reliable method for routine preimplantation and general prenatal sex determination in man.