In the present study, we examined the sequential changes of procoagulant activity (PCA) in different host and graft tissue compartments in order to assess its role as an immunologic effector and monitor of the rejection process. An early increase in PCA in the graft mesenteric nodes marks the onset of the host-graft immune interaction prior to any PCA or histologic changes in the other tissue compartments. This was followed by increases in PCA in the peripheral blood and graft intraepithelial compartments coinciding with maximal clinical and histologic signs of rejection. Cyclosporin A fully suppressed alloantigen-induced activation of PCA in the intraepithelial compartment and peripheral blood mononuclear cells, but only partially suppressed PCA in graft mesenteric nodes of the allogeneic transplants. The sequence of PCA changes accurately reflected the clinical and histologic changes during allograft rejection. Thus, PCA measured in peripheral blood mononuclear cells appears to be a sensitive and accurate marker of allograft rejection.