Noroviruses (NoVs) are the leading cause of viral gastroenteritis in humans of all ages. Challenge studies that used the NoV prototype strain Norwalk virus (NV) have shown that some individuals are not susceptible to infection, suggesting the absence of a receptor. Recent studies have identified histo-blood group antigens (HBGAs) as possible receptors. Being a nonsecretor and presence of HBGA type B were associated with protection against infection with NV, a genogroup (GG) I NoV.In the present retrospective study, we investigated the association between presence of HBGAs and the risk of infection with another NoV belonging to GGI (Hu/NV/I/Birmingham/93/UK). The study was done as part of an investigation of a waterborne outbreak in a group of schoolchildren and of a cohort of healthy adults. The ABH histo-blood group phenotype was determined by use of saliva or serum samples from these individuals.Presence of HBGA type B was significantly correlated with a lack of susceptibility to infection with GGI NoV and with an absence of antibodies. No correlation was found with GGII NoV. Although the infection rate in nonsecretors was lower, this difference was not statistically significant, and several children lacking HBGAs in saliva were found to be infected.Individuals with the HBGA type B may be protected against infection with GGI (but not GGII) NoVs. The association between susceptibility to NoV infection and being a secretor may be restricted to GGI NoV.