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The immunologic response of graft recipients to antilymphocyte globulin has been studied. The clearance from the serum of (125)I-labeled antilymphocyte globulin was studied in 15 graft recipients previously treated with antilymphocyte globulin and in 4 control patients not previously treated with antilymphocyte globulin. The mean serum half-life of antilymphocyte globulin was 7.2 days in control patients, 3.8 days in 13 renal graft recipients, and 22 hr in 2 heart graft recipients. All but one of the antilymphocyte globulin-treated patients had rapid clearance. Patients treated with equine antilymphocyte globulin had rapid clearance of rabbit and goat antilymphocyte globulin as well as horse antilymphocyte globulin. All patients with rapid clearance of antilymphocyte globulin had circulating antibodies to xenogeneic gamma globulin. Two patients with rapid clearance of antilymphocyte globulin had circulating complexes of antilymphocyte globulin. Five renal graft recipients were treated with aggregate-free equine gamma globulin before antilymphocyte globulin therapy in an attempt to induce tolerance to xenogeneic gamma globulin. In these five patients neither rapid clearance of antilymphocyte globulin nor significant titers of circulating antibody to xenogeneic gamma globulin developed. The induction of tolerance to xenogenic gamma globulin may benefit patients treated with antilymphocyte globulin.