Allogeneic stimulation of human lymphoid cells initiates a collaborative cellular pathway that relatively rapidly induces in monocytes the synthesis and cell surface expression of tissue factor, the initiating cofactor of the extrinsic coagulation pathway. T cells are required for the monocyte procoagulant generation, because the addition of autologous or allogeneic T cells fully reconstitutes the activity in otherwise nonresponding highly purified monocytes. Despite a strict T cell requirement, only low T cell to monocyte ratios are necessary for maximal PCA response. Our results further demonstrate that the collaborative signal from allogeneically stimulated T cells to effector monocytes is transferred by a soluble mediator rather than direct cell to cell contact. Other aspects of the present study include the observation that among normal peripheral blood lymphoid cells, monocytes elicit the strongest allogeneic PCA response. This response is clearly exceeded by that induced upon stimulation with Daudi lymphoblastoid B cells. Our data demonstrate the existence of a second distinct cellular pathway that mediates the lymphoid procoagulant response. This pathway differs from the previously characterized response to bacterial LPS in respect to: a) kinetics of T cell triggering; b) mediation by a soluble product; c) lack of genetic restriction of T cell; monocyte collaboration; and d) deficient capacity for direct T cell induction of the monocyte PCA response.