Sera from 12 multitransfused patients who were refractory to random-donor platelets were tested for lymphocytotoxic and leukoagglutinating antibodies using panel cells from various volunteers whose HLA-A and -B antigens were known. All sera contained leukoagglutinins reactive with cells from at least one panel member, whereas only 33% had lymphocytotoxic antibodies. Patients whose sera reacted frequently with panel cells using the microcapillary agglutination technic seldom responded to HLA-matched paltelets, whereas those whose sera reacted infrequently usually responded satisfactorily. It is concluded that non-HLA antibodies may play a significant role in determining the responses to platelet transfusions in multi-transfused patients.