The expression of tissue factor activity was evaluated in homogenates and in intact whole cells from a variety of human and nonhuman cell lines of normal and neoplastic origin. A high degree of species specificity in the interaction of tissue factor with other coagulation factors was observed in guinea pig, rat, mouse, and hamster cells. Tissue factor was present in significant amounts in homogenates of both the normal and neoplastic cells tested in all four species examined. No correlation was observed between the amount of tissue factor detected in cell homogenates and the derivation of the cell line from normal versus neoplastic tissue. Intact cells also expressed tissue factor activity, but lower levels were found in most cell lines examined. The significance of these data is discussed with regard to fibrin deposition around tumors in vivo.