The nature of the cells required for first-set graft rejection in vivo was examined by using an adoptive transfer system to restore heart-graft rejection in irradiated rats. Highly purified inocula of peripheral T lymphocytes were shown to quantitatively account for the restorative ability of adoptively transferred cells. These T cells were shown to be long-lived small lymphocytes which are not recently derived from the thymus during adult life. They belong to the pool of T cells which constantly recirculate from blood to lymph as shown by their rapid appearance in the lymph of iradiated syngeneic rats after intravenous injection. Neither B lymphocytes nor antibodies in the circulation or in the graft itself are required for first-set graft rejection.