Rabbits were immunized with suspensions of lymph node cells from A/Jax mice. The resulting antiserum (RAMLS) contained antibodies to A/Jax lymph node cells, demonstrable as cytotoxins and agglutinins, and antibodies to other mouse tissues and mouse serum proteins demonstrable as precipitins. The RAMLS caused a specific lymphopenia when given to mice. Absorption of antibodies to nonlymphatic mouse tissues and to mouse serum proteins did not alter the cytotoxic or agglutinating effect of the RAMLS on lymphocytes and did not alter the in vivo lymphopenic effect. Chronic administration of RAMLS resulted in sustained lymphopenia during the period of serum treatment without significant morbidity or mortality. Mice chronically treated with RAMLS do not make antibody to rabbit γ-globulin as readily as those given normal rabbit serum. Histologic studies of mice chronically treated with RAMLS show depletion and destruction of tissue lymphocytes in lymphoid organs. A similar state of profound lymphocyte depletion can be achieved by a short, intensive course of RAMLS treatment.