OBJECTIVE: The aim of this study was to develop a new experimental model of antiplatelet autoimmune disease in the mouse. MATERIALS AND METHODS: Mice were immunized with rat platelets. Anti-mouse platelet autoantibody responses were analyzed by enzyme-linked immunosorbent assay, Western blots, and flow cytometry. RESULTS: Immunization of CBA/Ht mice with rat platelets was followed by a transient thrombocytopenia. Platelets were opsonized by autoantibodies that recognized both rat and mouse normal platelets and (then) destroyed by phagocytosis. Absorption experiments indicated that these autoantibodies reacted with epitope(s) shared by rat and mouse platelets. In contrast, BALB/C mice similarly immunized with rat platelets did not develop thrombocytopenia. The ability of BALB/C mice to produce anti-rat platelet antibodies and to eliminate antibody-coated platelets was comparable with that of CBA/Ht animals. However, the specificity of the antibody response elicited in these two mouse strains differed markedly, with a 145- to 155-kDa mouse platelet antigen corresponding to platelet glycoprotein Ib recognized in CBA/Ht, but not in BALB/C, animals. CONCLUSION: This immunization protocol may serve as a model of antiplatelet autoimmune response, especially of posttransfusion purpura.