Both aggregated IgG and soluble immune complexes composed of human serum albumin and specific antibody at a 4:1 ratio were demonstrated to rapidly induce an increase in procoagulant activity (PCA) of murine peripheral blood mononuclear cells. Direct cytologic assays as well as fractionation of cells by adherence to plastic established the monocyte as the cell producing PCA, and demonstrated further that almost all monocytes, rather than a subpopulation, participated in the response. Monocytes that were depleted of lymphocytes did not respond to these stimuli with production of PCA; that is, induction of monocyte PCA was observed only when stimulation was performed in the presence of lymphocytes. Induction was equally efficient when only the lymphocyte was stimulated by aggregated IgG or soluble immune complexes, washed free of unbound stimulus, and added to monocytes. This suggests a unidirectional pathway by which the stimulus triggers lymphocytes after which there is direct lymphocyte-mediated induction of monocytes to produce PCA. Evidence for participation of soluble lymphocyte products was not obtained, and it is suggested that this series of events may be mediated by direct lymphocyte contact with responding monocytes. The role of this pathway in the genesis of immunologically initiated tissue lesions is discussed.