The first two patients with post-transfusion purpura (PTP) due to platelet antibodies against the Zwb antigen are reported. The anti-Zwb specificity could be demonstrated only with an enzyme-linked immunosorbent assay (ELISA) but not with the immunofluorescence or the complement fixation test due to coexistent potent multispecific HLA antibodies. One of the patients had never received blood transfusion until 24 d before the development of thrombocytopenic purpura. In both patients, anti-Zwb of IgG1 and IgG3 subclasses defined by monoclonal antibodies were present during the thrombocytopenic period but the antibodies of IgG3 subclass disappeared concomitantly with clinical improvement. The association between the IgG3 subclass of anti-Zw antibodies and the destruction of autologous platelets in Zw-immunized individuals was investigated further. All of four PTP patients had anti-Zw antibodies of the IgG1 and IgG3 subclasses during the thrombocytopenic period while all of 20 mothers of children affected with alloimmune neonatal thrombocytopenia (AINT) had anti-Zwa of only the IgG1 and not IgG3 subclass at the time of delivery of thrombocytopenic children (P less than 10(-4). Thus, the destruction of autologous platelets in PTP is associated with the presence of anti-Zw of the IgG3 subclass which may be of importance in the pathogenesis of PTP.