Tissue factor is a cellular receptor that initiates blood coagulation. The TF gene is constitutively expressed in some extravascular cell types and is inducibly expressed in several vascular cell types, including monocytes, vascular endothelial cells and vascular smooth muscle cells. Functional studies indicate that Sp1 controls basal TF gene expression. A distal enhancer (-227 to -172) containing two AP-1 sites and an NF-kappa B site mediates induction of the human TF promoter in monocytic cells and endothelial cells. Similarly, two AP-1 sites (-220 to -200) regulate induction of the murine TF promoter in fibroblast-like cells. In contrast, proximal enhancers in the human TF (-109 to -59) and rat (-103 to -80) TF promoters containing Egr-1 and Sp1 sites mediate induction in epithelial-like cells and vascular smooth muscle cells, respectively. These results suggest that cell type-specific pathways regulate TF gene expression.