Platelet transfusions are life saving treatments for many patients with thrombocytopenia, however, their use is generally discouraged in the autoimmune disorder immune thrombocytopenia (ITP). We examined whether allogeneic platelet major histocompatibility complex (MHC) class I transfusions affected anti-platelet CD61-induced ITP. BALB/c CD61 knockout (KO) mice (CD61-/H-2(d)) were immunized against platelets from either wildtype syngeneic BALB/c (CD61+/ H-2(d)) or allogeneic C57BL/6 (CD61+/ H-2(b)) or C57BL/6 CD61 KO (CD61-/ H-2(b)) mice and their splenocytes were transferred into severe combined immunodeficient (SCID) mice to induce ITP. When non-depleted splenocytes were transferred to induce antibody-mediated ITP, both CD61+ platelet immunizations generated immunity that caused thrombocytopenia independently of allo-MHC molecules. In contrast, when B cell-depleted splenocytes were transferred to induce T cell-mediated ITP, transfer of allogeneic MHC-immunized splenocytes completely prevented CD61-induced ITP development. In addition, allogeneic platelet transfusions into SCID mice with established CD61-induced ITP rescued the thrombocytopenia. Compared with thrombocytopenic mice, bone marrow histology in the rescued mice showed normalized megakaryocyte morphology and in vitro CD61-specific T cell cytotoxicity was significantly suppressed. These results indicate that antibody-mediated ITP is resistant to allogeneic platelet transfusions whereas the T cell-mediated form of the disease is susceptible suggesting that transfusion therapy may be beneficial in antibody-negative ITP.