A 55-year-old woman with common variable immunodeficiency and mild chronic obstructive lung disease received 3 units of plasma as immunoglobulin replacement therapy. During the administration of the final unit, her temperature rose 1 degree C, with no other observable symptoms. Fifteen minutes later she developed shortness of breath without nausea, vomiting, rash, or pruritus. In 30 min she lost consciousness, was breathless, and cyanotic. Resuscitative efforts failed. Autopsy failed to pinpoint a cause of death. There was no evidence of ABO or Rh incompatibility, bacterial contamination, or hemolysis. There were no neutrophil, platelet or IgA antibodies detectable in the patient or the 3 plasma donors. There were no lymphocytotoxic HLA antibodies in the patient or two of the plasma donors. The third donor had HLA-B35 lymphocytotoxic antibodies that did not agglutinate or aggregate neutrophils. The patient's HLA type was A2, A3; B35, B40. Lymphocytotoxic crossmatches using lymphocytes of the patient were positive with plasma from the third donor but negative with the other two. An eluate prepared from post-mortem lung parenchymal tissue was cytotoxic to 7 of 8 panel lymphocytes positive for the HLA-B35 antigen but not with cells lacking B35. The implicated plasma donor was healthy with a history of 6 pregnancies. This case report illustrates the potential hazard of transfusion of plasma containing HLA antibodies.