To evaluate whether immunological enhancement plays a role in adaptation to renal allografts, we studied sera from transplant recipients to determine whether those which suppressed mixed leukocyte culture (MLC) responses in vitro contained alloantibodies reactive with donor cells. Sera from five of nine renal transplant recipients consistently and specifically suppressed autologous autologous MLC responses to donor cells without impairing the blastogenic responses to third-party leukocytes, soluble antigens, or nonspecific mitogenic agents. In three of the five cases the suppressive activity of the serum was striking; in two cases the effect was less marked but still readily demonstrable in studies designed to evaluate the dose of serum which provided optimal suppression of MLC responses. Serum from one of the recipients nonspecifically suppressed blastogenic activity both to donor cells and other stimuli. No alloantibody reactive with donor leukocytes was found in any of the sera which exhibited suppressive activity in MLC, whereas in one patient, serum which contained antibody reactive with donor cells did not suppress MLC response to that donor. These findings suggest that, if the serum factors which suppress MLC responses in vitro are enhancing antibodies, they are not detectable even with very sensitive techniques either because they are present in very low concentrations, belong to immunoglobulin classes other than IgA, IgG, or IgM, or are complexed with donor antigen in such a way that their ability to react with fresh donor cells in vitro is blocked.