We have isolated cDNA clones from a human fetal brain library that encode five members of the EPH sub-family of receptor protein tyrosine kinases (PTKs). Comparison of the DNA sequences of these receptors to the Genbank database reveals that two of our clones correspond to the previously identified HEK and ERK receptors, two are apparently human homologues of the mouse receptors Sek and Bsk and one is novel. With these additions, the number of known human EPH sub-family members is nine and the total in all vertebrate species is 13 making it the largest known sub-family of PTKs. Analysis of the expression pattern of EPH sub-family mRNAs reveals that some are expressed in a wide variety of adult tissues while others are quite restricted. Consistent with the amplification of these sequences from a fetal brain cDNA library, all five members which we have isolated are expressed in the brain. We have named these receptors HEK4, HEK5, HEK7, HEK8 and HEK11, following the nomenclature of Wicks et al. (1992) and the numbering convention set forth by Sajjadi et al. (1991). Analysis of these new EPH sub-family members will increase our understanding of the biology of this receptor family and their isolation will provide reagents for the identification of ligands for this large family of orphan receptors.