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Hawaii virus (HV), from a 1971 family outbreak of gastroenteritis, is serotypically distinct from Norwalk virus (NV), recently identified as a human calicivirus by molecular analysis. About 2600 consecutive nucleotides of the HV genome (including those encoding the viral capsid protein) and part of the polymerase region of three other viruses (MDV1, MDV6, and SV7) were sequenced. Comparison of the amino acid sequence of the capsid protein of HV with NV and other human caliciviruses (Toronto virus [TV24], Desert Shield virus [DSV395], and Southampton virus [SHV]) demonstrated the existence of two major genetic groups (genogroups) typified by HV and NV. HV had 76% identity with TV24 and 48% identity with NV, DSV395, or SHV. In addition, comparison of part of the polymerase protein of HV with other human caliciviruses also showed that there were these two genogroups. The large genetic diversity between the capsid sequence of HV and NV is consistent with their serotypic distinctiveness.