Tissue factor (tissue thromboplastin, coagulation factor III), a protein component of cell membranes, is an essential cofactor for factor VII-dependent initiation of blood coagulation. Since no tissue factor-deficient condition has been described, it is one of only a few proteins of the coagulation system for which the pattern of inheritance has not been ascertained. Because of the species-specificity of tissue factor activity and the availability of a very sensitive chromogenic assay, it was possible in the present study to use somatic cell hybrids to assign the chromosomal location of the tissue factor structural gene (F3) to human chromosome 1 (1pter----1p21).