The results of this radioautographic study demonstrated that ALS destroys large numbers of the long-lived small lymphocytes. Morphologic evidence of destruction was apparent in measenteric lymph nodes and was reflected by reduced numbers of long-lived cells in the thoracic duct lymph. In addition, this agent stimulated some long-lived small lymphocytes to transform into large blast cells. Little, if any, change was noted in the cell content of the thymus and bone marrow, tissues known to contain large numbers of short-lived small lymphocytes. A maximum reduction in the number of long-lived cells was seen by 24 hr after the first injection of ALS and subsequent daily injections for 7 days did not appear to enhance the effect. Although blood lymphocyte levels returned to normal within 6 weeks after cessation of ALS treatment, the number of small lymphocytes in TDL reached only 50% of the control levels. Throughout the experiments normal numbers of short-lived small lymphocytes continued to appear in the TDL of ALS-treated rats. The results are discussed with respect to the immunosuppressive action of ALS.