Previously, we have identified two immunological responses associated with protection from infection in norovirus-challenged volunteers. An early (day 1-3) post-exposure salivary IgA response in genetically susceptible volunteers correlated with protection from Norwalk virus infection [54] and an early T h 1 response correlated with protection from Snow Mountain virus infection [44] . Historically, the role of IgG in norovirus protection has been unclear. By adulthood, .90% of the population [48] is positive for anti-norovirus IgG, and norovirus strains within a genogroup share a high degree of antigenic cross-reactivity as measured by EIA [44, 60] . These facts likely skew functional interpretations of the role of serum IgG titers on susceptibility to infection and/or infection outcomes. Although carbohydrate ligand blockade antibody responses have been suggested as correlates of protective immunity [13, 35, 36] , it wasn't until recently that these blockade responses were correlated definitively with protection from clinical disease and infection [10, 38] . Importantly, our surrogate neutralization assay is specific enough to differentiate GII.4 norovirus strains too similar to be distinguished by EIA but different at key antigenic sites. While human re-challenge studies using the same viral inoculum are necessary to confirm an association between a blockade IgG response and protection from repeat norovirus infection, our findings support the clinical relevance of the antibody blockade assay as a correlate of protective immunity [38] .