Three HLA-specific antisera were comparatively analyzed by platelet microcomplement fixation and 14C-serotonin uptake and/or 14C-serotonin release studies with platelets. In general, there was a good correlation of HLA antibody specificity exhibited in all 3 test systems. Quantitative differences in the response of platelets to HLA antisera were observed and accounted for by differences in antigen density and different types of antibodies involved. Platelet autoantibodies could not be detected by means of 14C-serotonin release from platelets in plasma.