Angiogenesis, the process by which new blood vessels are formed, is essential in reproduction, development, wound repair and oncogenesis. Endothelial receptor tyrosine kinases are likely to play key roles in the intercellular signalling controlling angiogenesis. We have here analysed the expression of the endothelial receptor tyrosine kinase tie during the earliest stages of vascular development. The mouse tie cDNA was isolated and sequenced and the exon structure of the coding region was determined. The part of the tie gene encoding the extracellular domain was found to be organized in exons specifying the characteristic domains of the Tie polypeptide. Early postimplantation mouse tissues were analysed for tie expression by in situ hybridization. No tie mRNA was detected in 7.5 day mouse embryos. In 8.5 day embryos, tie expression was observed in differentiating angioblasts of the head mesenchyme, in the splanchnopleure and dorsal aorta as well as in migrating endothelial cells of the developing heart. A weak tie signal was also obtained from angioblasts in the blood islands of the yolk sac. Furthermore, tie mRNA was prominent in the endocardium of the embryo and in the endothelial cells forming the lung vasculature. Expression of tie persisted in the lung capillaries of adult mice, but was decreased in the endocardium. These results suggest that the tie receptor tyrosine kinase is involved in angiogenesis and/or maintenance of endothelial cell functions.