ZFY is a candidate for the primary sex-determining gene (TDF, testis-determining factor) on the human Y chromosome. We have isolated cDNA clones of ZFY and its homologue on the X chromosome, ZFX. The transcripts of these genes are very similar to each other and encode predicted proteins of equal size. The conceptual amino acid sequence of both proteins contains an acidic domain, similar to the activation domain of transcription factors, and a potential nucleic acid-binding domain of 13 "zinc fingers." We have used the polymerase chain reaction to demonstrate the expression of ZFY and ZFX in a wide range of adult and fetal human tissues and to show that ZFX is expressed from the inactive X chromosome present in human-mouse hybrids.