Noroviruses (NVs) are common pathogens that consist of genetically divergent viruses that induce gastroenteritis in humans and animals. Between September 1999 and June 2004, 1,898 samples obtained from patients showing sporadic or outbreak gastroenteritis in Chiba Prefecture, Japan, were tested for NVs by reverse transcription-PCR. NVs were detected in 603 samples. Approximately 80% were positive for genogroup GII, 13% were positive for genogroup GI, and the remaining 7% were positive for both genogroups. Phylogenetic analysis showed that the GI and GII genogroups could be further divided into 13 and 16 genotypes (including new genotypes), respectively. The GII-4 genotype, which included five small genetic clusters (subtypes), was the most common in this study and was detected in approximately 40% of positive samples. The P2 regions of 10 strains belonging to each of the five GII-4 subtypes showed 5 to 18% amino acid diversity. The amino acid substitutions accumulated in the protruding (P) region during the 5-year study period. Our data suggest that highly variable NV strains are circulating in Chiba Prefecture, with a high rate of genetic change observed during the 5-year study period.The genus Norovirus is a member of the family Caliciviridae. Caliciviruses contain a positive-sense single-stranded RNA genome and include a further three genera, Vesivirus, Lagovirus, and Sapovirus (2,3,8). Noroviruses (NVs) have three major open reading frames (ORFs) that encode nonstructural, capsid, and minor structural proteins, respectively (8). They are one of the most common causes of gastroenteritis and have been detected in fecal samples from both humans (12,15,28) and animals (20,30,37). Human-associated NV outbreaks resulting from ingestion of contaminated water or food, such as oysters (4,5,18,23), and outbreaks in public places, particularly hospitals, schools, and cruise ships (9,11,22,36), pose an important public health problem.Reverse transcription-PCR (RT-PCR) and sequencing of the partial viral genome are the most popular and useful procedures for obtaining epidemiological and genetic information on NVs. Human NVs can be divided into two genogroups, genogroups GI and GII, by genetic analysis of the RNA polymerase and capsid regions (1, 15), with several genotype classifications having been reported independently (1,16,33). Recently, based on the genotype classification of Katayama et al. (16), Kageyama et al. (15) reported on a detailed scheme for the genotyping of NVs based on distribution analysis by using the pairwise distance of the capsid N-terminal/shell domain. They classified the GI and GII genogroups into 14 and 17 genotypes, respectively.During the winter of 2002-2003, an increase in NV outbreaks was reported in Europe and the United States (6, 21). Moreover, worldwide, the GII-4 genotype (Bristol virus-like genotype) has been shown to be the predominant strain of NV associated with gastroenteritis (13,21,(34)(35)(36). Changes in the phylogenetic and genetic characteristics of GII-4 genotype strains...