Platelet concentrates from HLA-compatible donors frequently provide satisfactory posttransfusion platelet responses in patients who, for immunologic reasons, are refractory to pooled random-donor platelet transfusions. The use of donors who have HLA antigens "crossreactive" with those of the recipient has increased the number of donors available for individual patients. Occasionally, successful transfusions occur with donors mismatched for HLA. Immunologic explanations include a restricted pattern of HLA antibody production and a variable expression of HLA antigens on the platelet surface. Immunologic reasons for poor response to HLA-matched transfusions include ABO incompatibility, antibodies directed against platelet-specific antigens. HLA-Bw4/Bw6 incompatibility, and as yet undefined incompatibilites. The one-hour posttransfusion platelet count may be useful in identifying patients who are alloimmunized and have non-immunologic reasons for shortened platelet survival such as fever, sepsis, or a coagulopathy. Caution must be used in evaluating results of currently available platelet crossmatch tests.