The tetraspanins, also known as members of the transmembrane 4 superfamily (TM4SF), comprise an assemblage of surface antigens reported from mammalian and other vertebrate cells, from schistosomes, from fruit flies and from Caenorhabditis elegans. Tetraspanins are characterized by the presence of four hydrophobic domains, which are presumed to be membrane-spanning, and specific conserved motifs. A novel cDNA encoding a new tetraspanin, termed TE736 (tetraspanin 736), was isolated and characterized from the human blood fluke Schistosoma japonicum. Nucleotide and deduced amino acid sequences of the cDNA revealed that TE736 was similar to the previously characterized Sm23/Sj23/Sh23 species homologues and to Sj25/TM4 from schistosomes, and to other tetraspanins. Comparison of hydropathicity profiles of TE736, Sj25/TM4 and two novel tetraspanin-like sequences from S. mansoni showed that they contain four potential transmembrane domains like other tetraspanins. Sequence alignments showed there are four highly conserved, cysteine residues on the second predicted extracellular loop of TE736. A phylogenetic comparison of the relationship of approximately 30 tetraspanins from mammals and other groups revealed that TE736, Sj25/TM4 and the two sequences from S. mansoni formed an independent family of tetraspanins. We have termed these tetraspanins from schistosomes the Sj25 family. TE736 appeared to be encoded by a single gene and to be expressed in at least two life cycle stages of S. japonicum.