Using a polymerase chain reaction-mediated approach we have characterized cDNAs from human and mouse origin representing a novel type of receptor protein tyrosine kinase (RTK). The deduced amino acid sequence (855 amino acids) of the longest open reading frame has a unique extracellular region encompassing a factor VIII-like domain, not previously described for RTKs. The most closely related RTKs are members of the neurotrophin receptors (TRK), which showed 47-49% homology with the kinase domain of the new RTK. Therefore, the new gene has been called TKT (Tyrosine-Kinase related to TRK). TKT orthologs from man and mouse were 98% similar. In both species a major transcript of 10 kb was found to be expressed at high levels in heart and lung. Low levels of this mRNA-species were detected in human brain, placenta, liver, skeletal muscle, kidney and in mouse brain and testis. Analysing human/mouse somatic cell hybrids we demonstrated that TKT segregates with human chromosome 1.