To examine the roles of the eph subfamily of receptor tyrosine kinase (RTK), we isolated mouse cDNAs for sek, elk, and eck and localized their mRNAs in the developing mouse, with particular reference to the CNS development, by in situ hybridization. sek mRNA is most abundantly expressed throughout development; sek was detected in the germinal layer of the embryonic CNS during mid- to late-gestation and was widely expressed in the early postnatal brain. elk was expressed in the mantle layer of the embryonic CNS and showed a distribution complementary to that of sek. Differential expression of sek and elk was also observed in the early postnatal cerebellum; sek was expressed in the Purkinje cells, while elk was detected in the granule cells. eck was moderately expressed in the germinal layer of the embryonic CNS at mid-gestation, but its expression decreased as development proceeded. These spatio-temporally different patterns of gene expression suggest that these RTKs have distinct roles in mouse development despite their structural homology.