We have isolated rat cDNAs that encode two related receptor-like tyrosine kinases. One of these receptors, TIE-1, is the rat homolog of a recently described human receptor-like kinase termed TIE (Partanen et al., 1992). The related TIE-2 receptor has the same organization of amino acid sequence motifs characteristic of TIE-1: two immunoglobulin-like domains, three epidermal growth factor (EGF)-like domains and three fibronectin III-like repeats in the extracellular region and a short kinase insert sequence and C-terminal tail in the intracellular region. The amino acid sequences of the intracellular and extracellular regions of TIE-1 and TIE-2 are 79% and 32% identical respectively. Both tie genes are broadly expressed in embryonic, neonatal and adult tissues, accounted for largely by their coexpression in endothelial cells. The tie-2 gene is also uniquely expressed in several additional embryonic tissues, including the lens epithelium and the heart epicardium.