Noroviruses are the major viral pathogen of epidemic acute gastroenteritis. Two outbreaks of norovirus gastroenteritis that occurred in China in 2003 and 2006, caused by a GII-4 and a GII-3 strain, respectively, were studied to investigate potential association between viral infection and histo-blood types of hosts. The histo-blood group antigen (HBGA) phenotypes of 146 subjects (16 from the GII-3 and 130 from the GII-4 outbreaks) were determined in a saliva-based EIA. Our results showed that the secretor status of individuals was strongly associated with infection in the two outbreaks (P=0.0007, OR=0.044, 95% CI, 0.003-0.765); none of the nonsecretor in either outbreak developed symptomatic infection. The infection rate of individuals with the ABH and Lewis blood types varied between the two outbreaks. In the GII-4 outbreak, association of ABH blood types with noroviral infection (P=0.001, Chi-square=16.13) has been observed, in which the type A individuals had an increased risk of infection [61% in the symptomatic group (n=41) vs. 30% in the asymptomatic group (n=89), P=0.0001], while the type O individuals showed a decreased infection rate (17% vs. 48% in the two groups, P=0.0048). In the GII-3 outbreak, however, individuals with the H antigen only appeared to have a higher rate of infection (33% vs. 14%, P=0.059). Our study provided further evidence in the association between noroviral infection and the HBGA types of hosts. While the nonsecretor phenotype appears naturally resistant to these two strains, additional determinants on the HBGAs also may play roles in host range of the two strains.