Members of the protein superfamily of transmembrane receptor tyrosine kinases are key components of intercellular signal transduction pathways that elicit appropriate cellular responses to environmental cues during development of multicellular organisms. In a search for additional receptor tyrosine kinases expressed during mouse embryogenesis we cloned the murine homolog of Eck, a member of the Eph subfamily, that maps to the distal region of mouse chromosome 4. Specific antisera defined Eck in murine embryonic cells as a glycoprotein of 130 kDa with an intrinsic autophosphorylation activity. Immunohistochemical staining and laser scanning microscopy revealed a dynamic and tightly regulated distribution of Eck receptor protein in the developing mouse embryo. During gastrulation, a high transient distribution of Eck was seen in mesodermal cells aggregating in the midline as notochordal plate. A similar restriction of Eck receptor protein was apparent along the rostrocaudal axis of the developing neural tube. In hindbrain neuroepithelia, Eck protein localised specifically to cells of rhombomere 4 and was also seen transiently in cells populating second and third branchial arches and neurogenic facial crest VII-VIII and IX-X. Receptor distribution also implicated Eck in development of the proximodistal axis of the limb, expression being restricted to distal regions of limb bud mesenchyme. At later stages, additional sites of Eck protein expression were seen in the cartilaginous model of the skeleton, tooth primordia, infundibular component of the pituitary and various fetal tissue epithelia. Taken together, our data suggest pleiotropic functions for the Eck receptor, initially in distinctive aspects of pattern formation and subsequently in development of several fetal tissues, and reveal possible allelism with known mouse developmental mutant loci.