We have isolated cDNA clones encoding Tyro 10, a novel receptor protein-tyrosine kinase (PTK) whose catalytic domain exhibits significant similarity to the Trk family of neurotrophin receptors (Lai & Lemke, 1991). We find that the Tyro 10 gene is widely expressed, both within and outside the nervous system, and in both developing and mature neural tissue. The primary structure of Tyro 10, deduced from cDNA sequence, defines a new sub-family of receptor PTKs. Although the Tyro 10 kinase domain is more closely related to the equivalent domains of Trk, TrkB and TrkC than to the catalytic domains of other receptor PTKs, it is less closely related to these Trk domains than they are to each other. More significantly, the Tyro 10 extracellular (ligand binding) domain is not structurally related to the extracellular domains of the Trk receptors, but instead bears homology to cell surface mediators of protein-protein interactions, including blood coagulation Factors V and VIII, and the neuronal recognition protein A5. These appear to be structural features of a distinct receptor PTK sub-family, in that they are also found in the recently-described discoidin domain receptor (DDR).