Endothelial protein C receptor (EPCR), present on endothelial cells of relatively large veins and arteries, plays a role in the enhancement of protein C activation by the thrombin-thrombomodulin complex. In the present study, we determined the organization and the complete nucleotide sequence of the human EPCR gene using polymerase chain reaction-direct sequencing method. The transcription initiation site of the EPCR gene was also determined by the cap site hunting method, using a cap site cDNA prepared from human placenta. The human EPCR gene spanned approx. 6 kb and was composed of four exons and three introns. All exon-intron boundaries agreed with the GT-AG rule. The 5'-flanking region (300 bp) of the EPCR gene contained a putative AP1-binding site, two Sp1-binding sites and two AP2-binding sites, but not definite TATAA or CCAAT sequences. Fluorescence in situ hybridization analysis showed that the EPCR gene is located in chromosome 20q11.2.