Hepatitis E virus (HEV) is a major cause of hepatitis. We evaluated five HEV antibody diagnostic assays by using outbreak specimens. The Abbott immunoglobulin G (IgG), Genelabs IgG, and Walter Reed Army Institute of Research (WRAIR) IgM assays were about 90% sensitive; the Abbott IgG and WRAIR total Ig and IgM assays were more than 90% specific.Hepatitis E virus (HEV) is the principal cause of acute hepatitis on the Indian subcontinent, in southeastern and central Asia, in the Middle East, in Mexico, and in parts of Africa. It is associated with the consumption of fecally contaminated drinking water (7,8,12,15). Recent outbreaks have occurred in Iraq, Chad, Sudan, and India (2, 9). Although HEV is associated with a low case fatality rate in the general population, pregnant women in the second and third trimesters are at greater risk (case fatality rates of 10 to 24%) for fulminant hepatitis and fetal loss (14, 18).HEV has not been cultured in vitro, and most enzyme immunoassays (EIAs) for HEV infection are based on either recombinant HEV proteins or synthetic peptides. These assays have varied significantly (16), and assays based on open reading frame 2 (ORF2) were shown to be more sensitive in detecting anti-HEV than those based on ORF3 (1,11,17). These recombinant-protein-based tests have detected anti-HEV in 90 to 95% of symptomatic HEV cases (3,10