Small amounts (0.5-2 .mu.l) of H-2-incomptaible blood given 16 days before skin grafting led to the induction of a long-lived unresponsiveness when the mice were given a short postoperative course of alternating doses of procarbazine hydrochloride and antilymphocyte serum. This unresponsiveness, which was specific for the blood donor strain, was wholly attributable to the white cell moiety, plasma and red blood cells having proved to be ineffective. The optimal dose range of white blood cells was fairly narrow (7 .times. 103-1.4 .times. 104). Of the various attempts made to demonstrate that the blood inoculum modified the response of normal mice, only direct skin grafting gave a positive result in that allogeneic skin graft survival was curtailed. Blood mixtures from several mouse strains injected into CBA recipients induced long-term unresponsiveness to skin grafts of the blood donor strains. Although it was possible to create unresponsiveness to DBA/2, C57Bl, or strain A skin grafts in CBA mice pretreated with blood from a closed colony outbred strain (TO), this pretreatment had no beneficial effect on TO skin grafts survival. TO blood failed to induce unresponsiveness to TO skin grafts in TO recipients. These findings are not necessarily inconsistent with the observation that, in inbred animals, the unresponsiveness induction was strain specific.