Ethylene oxide (ETO) is used to sterilize hemodialyzers and other medical equipment. In an attempt to confirm a link between ETO and hypersensitivity reactions during hemodialysis (HD) we quantitated IgE and total antibody directed against ETO-altered human serum albumin (ETO-HSA) in the sera of 65 hemodialysis patients. In 24 patients who had experienced anaphylaxis during HD, the levels of IgE and total antibody against ETO-HSA were significantly higher than the corresponding levels in 41 patients who had not. Our data demonstrate an association between the presence of IgE and total antibody against ETO-HSA and immediate anaphylactic reactions to HD. In further studies we characterized the ETO-HSA antigen by immunoelectrophoresis, gel filtration chromatography, and cross-inhibition immunoassay. Our results suggested that ETO gas can alter HSA and induce new antigenic determinants on the molecule. Recently, we encountered a peritoneal dialysis patient with rash and eosinophilia. Suspecting ETO allergy, we measured serum IgE and total antibody to ETO-HSA and found both to be present. The data suggest that, in addition to the familiar HD reactions, ETO sensitization might cause other allergic diseases as well.