In a search for novel tyrosine kinases involved in vertebrate development, we have isolated cDNAs corresponding to three distinct members of the Eph-family of receptor tyrosine kinases. Whole mount RNA in situ hybridization analysis showed all three genes were most abundantly expressed in the developing nervous system. zek1 (zebrafish Eph-like kinase1) encodes a 981 amino acid polypeptide closely related to the murine Sek1 and Bsk receptors. Cos-1 cells transfected with zek1 produce a 141 kilodalton tyrosine phosphorylated protein which is recognized by antibodies raised against two predicted Zek1 peptides. These antibodies also recognized a protein of the same apparent molecular weight in lysates from zebrafish embryos and adults. Widespread expression of zek1 in the developing brain and neural tube suggested a generalized function of the Zek1 receptor in neuronal cell ontogeny.