The induction of macrophage procoagulant activity by specific antigens is a close in vitro correlate of delayed-type hypersensitivity (DTH) reactions and provides a quantitative and sensitive measure of cell-mediated immune responses. The reaction is mediated by lymphokines from activated T lymphocytes and is potentiated by bacterial lipopolysaccharide. Lymphokines directly activated procoagulant activity on some murine and human macrophage tumor cell line cells although others required the collaboration of T lymphocytes, in the presence of lymphokine, to express activity. Macrophages in different stages of differentiation may vary, therefore, in their response to lymphokines. Pharmacological agents which regulate DTH reactions also mediated either the ability of lymphocytes to produce macrophage procoagulant inducing factor or the response of macrophages to the factors. Histamine and an anticoagulant found on stimulated T lymphocytes may be important regulatory mediators of macrophage procoagulant activity in vivo.