The antigenic relationship between viral isolates from Apodemus and Rattus that appear to cause the classical and mild types of epidemic hemorrhagic fever (EHF) in China was studied by cross-immunofluorescence, cross-neutralization, immunofluorescence blocking tests, and cross-enzyme-linked immunosorbent assay (ELISA). Obvious antigenic diversity between the isolates was demonstrated by cross-neutralization, immunofluorescence blocking tests, and cross-ELISA. Antisera from patients with classical EHF neutralized viruses of both types to a similar degree, but antisera from patients with mild EHF showed little neutralization of apodemus virus. Similarly, antisera from classical EHF blocked immunofluorescence by monoclonal antibody (25-1 McAb) derived from apodemus virus to both viral antigens, but antisera from mild EHF gave only low-grade blocking against apodemus viral antigen. Direct antigenic titrations of both viral strains by cross-ELISA yielded similar results. That distinct antigenic differences exist between viral strains causing these two types of EHF might be of great importance to the serological differentiation of the viruses and the study of EHF vaccine.