During her 26th week of pregnancy a 20-year-old woman developed generalized pruritus, urticaria, flushing, tinnitus, and tachycardia during plasmapheresis with 5% human serum albumin (HSA) as adjunctive treatment for anti-Kell isoimmunization. The reaction was controlled with intravenous diphenhydramine. Despite pretreatment with diphenhydramine and betamethasone a subsequent attempt to perform plasmapheresis with infusion of 5% HSA resulted in a more severe reaction which progressed to respiratory distress. Intradermal skin testing with 5% HSA produced a 9 x 11-mm wheal and 17 x 21-mm erythema at 15 minutes. An enzyme-linked immunoassay was positive for IgE antibody to 5% HSA before and after dialysis for removal of Na caprylate. These results are consistent with an IgE-mediated basis for this patient's reaction to HSA.