A hemagglutination inhibition (HAI) assay to assess serum antibody responses following Norwalk virus (NV) infection was developed. HAI activity increased significantly in individuals experimentally infected with NV (n = 18) and correlated with antibody levels measured in a histo-blood group antigen (HBGA) blocking assay. Prechallenge HAI antibody levels also correlated with protection from the development of gastroenteritis (Mann-Whitney test, P = 0.02). The HAI assay is another assay suitable for the detection of antibody that correlates with protection from Norwalk virus-associated disease.