Although the value of HLA matching for the selection of platelet donors for patients refractory to random platelets is beyond doubt, even perfectly matched combinations sometimes fail to give a satisfactory transfusion response. With HLA typing and negative lymphocytotoxicity crossmatches, 35% of the platelet transfusions administered to 15 patients gave disappointing results (29 of 82). Additional crossmatching with the newly developed platelet fluorescence test described in this paper reduced the unexpected transfusion failures to 7% (6 of 82). Five of these failures were observed in one patient. The target of the antibodies detected with this platelet fluorescence test is not yet fully specified. It seems probable that both HLA and platelet-specific non-HLA antibodies were detected. No correlation of the results of platelet transfusions with the presence or absence of leukoagglutinating antibodies was found.