Mixed lymphocyte culture (MLC) tests on the cells of mice made fully tolerant to allogeneic tissues in neonatal life showed an absence of specific antigen-reactive cells. Similary, no cells cytotoxic in a chromium release test could be detected. The absence of reactivity in the tolerant populations could not be accounted for by either suppressor cell activity or serum blocking factors. By contrast, mice in which partial tolerance had been deliberately or inadvertently induced often possessed detectable numbers of MLC-reactive cells and, after grafting, their sera inhibited the MLC reactivity of normal cells. These results are discussed in terms of possible mechanisms of self tolerance.