A 28 year old white man with hemophilia A had, for several years, been successfully maintained on a home care program utilizing self-administration of factor VIII concentrates, but one such infusion resulted in severe anaphylaxis. An immunoglobulin E (IgE)-mediated hypersensitivity response was demonstrated by (1) the release of histamine from the patient's basophils in vitro upon challenge with several different lots of factor VIII concentrate; (2) immediate cutaneous response to commercial factor VIII, factor IX and cryoprecipitate; and (3) measurement of IgE antibodies against a commercial factor VIII preparation. A subsequent life-threatening hemorrhage required cautious infusion of another commercial lot of factor VIII concentrate. Despite pretreatment with antiallergic drugs and attempted desensitization, a moderately severe anaphylactic reaction was observed.