We have isolated a human thrombomodulin cDNA, and a human genomic clone containing the putative promoter domain, as well as the translated and untranslated regions of the endothelial cell receptor. The nucleotide sequence of the thrombomodulin cDNA allows us to provide a complete picture of the structure of this endothelial cell receptor, and to confirm its homology to the human low density lipoprotein receptor. The nucleotide sequence of the thrombomodulin gene suggests areas within the putative promoter domain that may be critical for regulating expression of the human endothelial cell receptor, indicates a potential signal peptide, and shows that no introns are present within the coding region. The overall organization of the human thrombomodulin gene is surprising because it represents an example of a gene that contains epidermal growth factor type B repeats and a membrane spanning region, which are not isolated within discrete exons.