Monocytes generate the procoagulant material tissue factor (TF) when mixed mononuclear cell cultures are stimulated with antigens, mitogens, or bacterial endotoxin in vitro. Optimal monocyte TF production has been shown to require the presence of lymphocytes in the culture system. We have investigated the nature of this lymphocyte requirement by stimulating monocytes grown in the presence of varying numbers of T lymphocytes. In addition, some monocytes were grown in the presence of conditioned media prepared from T lymphocyte cultures. The results of these studies have demonstrated two pathways for monocyte TF generation: a relatively T cell-independent pathway that can be stimulated by endotoxin or PPD and a highly T cell-dependent pathway that can be stimulated by PHA. In addition, the lymphocyte requirement for PHA-induced monocyte TF generation may be replaced by conditioned media from T cell cultures.