Sox is a large family of genes related to the sex-determining region Y gene (designated as the SRY gene). Sox genes encoding DNA-binding transcriptional factors are found in many animals and are involved in developmental events. In this study, we newly isolated and sequenced novel Sox cDNAs from African clawed frog (Xenopus laevis). Five clones isolated here were classified into four distinct Sox genes designated as xSox17alpha1, xSox17alpha2, xSox18alpha and xSox18beta. All four belong to a subtype of SOX family, type F. The cDNA xSox17alpha1 contains essentially the same nucleotide sequence as that identified as Sox17alpha in a previous work (Cell 91 (1997) 397), whereas xSox17alpha2 is a distinct gene with high homology to xSox17alpha1. The clones, xSox18alpha and xSox18beta, are highly homologous to each other over the entire nucleotide sequences. The xSox18alpha and xSox18beta genes encode 363 and 361 amino acids, respectively. Genomic Southern hybridization analysis showed the existence of two copies of the xSox18. Northern analysis indicated that the xSox18 gene was expressed in the spleen and kidney and the size of the transcript was estimated to be 2.4 knt. Electrophoretic mobility shift assays indicated that recombinant xSox18 polypeptide was capable of binding to the HMG consensus nucleotide sequence, AACAAT.