The protein C anticoagulant pathway plays a crucial role in the regulation of fibrin formation. Protein C is activated on the surface of endothelial cells by the thrombin-thrombomodulin complex with the stimulation of the endothelial protein C receptor. The levels of circulating activated protein C reflect in-vivo protein C activation, and a low level of activated protein C is a risk factor for venous thromboembolism. The objective of the study was to assess the relative contributions of genetic and environmental factors to the variation in the levels of activated protein C and protein C. Blood samples were collected from 126 individuals belonging to 19 Spanish families, and heritability and common household effect were estimated for protein C, activated protein C and its complexes with protein C and alpha1-antitrypsin. In addition, we calculated the genetic correlation between protein C and activated protein C phenotypes. Although all phenotypes showed significant heritability, activated protein C phenotype resulted in a very high heritability of 83%, which clearly shows that this phenotype is strongly influenced by the action of gene(s). Furthermore, the bivariant analyses of protein C and activated protein C phenotypes indicate that there is a high genetic correlation between them (0.74). Nevertheless, this correlation is counteracted by a negative environmental correlation (-0.54) resulting in a phenotypic correlation of 0.35. The presence of such strong genetic effects suggests that it will be possible to localize the loci that influence this phenotype and determine the contribution to the risk of thrombosis.