Antigenic potential of genetically-engineered human erythropoietin (EPO) was assessed in guinea pigs (active systemic anaphylaxis [ASA] ; passive cutaneous anaphylaxis [PCA]) and in vitro (hemagglutination test [PHA]). In ASA, EPO at 70~700 U/kg elicited a weak anaphylactic response tvhereas the positive control ovalbumin (OVA) did cause intensive responses leading to death in 40% animals. However, the extract of CHO cells, to which EPO gene was introduced, did not cause any symptom. In PCA and PHA tests, neither EPO nor CHO cell extract induced positive responses. OVA, in contrast, produced high titers in both PCA and PHA tests. It was concluded that, in light of the fact that EPO was slightly antigenic only in ASA but not in PCA or PHA and also that human EPO is a foreign protein to guinea pigs, the present EPO may not be antigenic in humans.