Studies carried out in our laboratory during the years indicated that the local xenogeneic graft-versus-host reaction (GVHR) might serve as a useful clinical assay of the immunocompetence of human T lymphocytes. Additional studies were therefore carried out using purified populations of B, T and null cells as well as normal mononuclear cell populations, so as to determine the nature of the cells responsible for induction of the reaction and further delineate the factors capable of modifying this pattern of reactivity. Populations of T cells alone gave the largest reaction whereas both B cells from patients with chronic lymphatic leukemia and null cells from patients with acute lymphatic leukemia failed completely to induce a GVHR. The addition of anti-T-lymphocytic serum abolished the reaction, providing further proof of the role played by T lymphocytes. Thymic hormone (THF) was found to enhance the reaction when applied both in vivo and in vitro. The immunostimulatory agents transfer factor and levamisole also enhanced the GVHR obtained with normal mononuclear cells. Cytoxan was found to have an enhancing effect at low doses and an inhibiting effect at high doses. Trypsin also acted to abolish the GVHR. The combination of two populations of normal mononuclears always gave a larger GVHR, indicating allogeneic antigen stimulation. Depletion of the monocytes from the population of normal mononuclears resulted in a smaller reaction, providing further evidence that monocytes are required for T-lymphocyte antigen-induced reactivity. On the basis of these findings it is proposed that the local xenogeneic GVHR is a useful clinical test for the measurement of immunocompetence of T lymphocytes, for the differential diagnosis of leukemias and for the determination of the effectiveness of THF.