The SRY (sex-determining region Y) gene encodes a transcription factor characterized by a DNA-binding motif termed the HMG (high mobility group) domain. The SOX (Sry-box) genes comprise a large family related by homology to the HMG-box region. We isolated a cDNA clone with an open reading frame encoding a putative protein of 384 amino acids, which shared 83% identity to the mouse Sox18 protein. Northern blot analysis revealed that a 1.9-kb band of human SOX18 messenger RNAs was predominantly expressed in heart, although weak signals were seen in brain, liver, testis, and leukocyte. By polymerase chain reaction (PCR)-based analyses with both a human/rodent monochromosomal hybrid cell panel and a radiation hybrid panel, the gene was mapped to the chromosome 20q13.33 region.