We have identified cDNA clones that encode a new member of the Eph receptor tyrosine kinase subclass by using antibodies to phosphotyrosine to screen a chicken embryonic cDNA expression library. These cDNAs were in turn used to isolate the entire coding sequence of this receptor from both mouse and chicken (designated Mek4 and Cek4, respectively). A cDNA that encodes a putative secreted form of the murine receptor's ligand-binding domain and lacks the transmembrane and kinase domains was also isolated. Analysis of the appropriate Mek4 genomic region revealed the presence of sequences required for the production of the secreted form of the receptor. Analysis of RNAs from various tissues shows the receptor to be highly expressed in mouse and chicken embryos, with the greatest levels of expression occurring in the brain. In adult mouse, the pattern of RNA expression is altered and appears to be confined primarily to the brain. However, a shorter transcript was found to be expressed at reduced levels in the testis. This new Eph-related receptor may play an important role during development and in signal transduction pathways.