The Sapporo-like human caliciviruses (HuCVs) comprise one of three genogroups of HuCVs associated with acute gastroenteritis. Phylogenetic analysis has shown that Sapporo-like HuCVs are related more closely to animal caliciviruses than to other known HuCVs. We produced 3.2 kb cDNA fragments from the 3' end to three Sapporo-like HuCVs that were associated with acute gastroenteritis in children (Houston/86, Houston/90, and London/92). Sequence analysis of the 3.2 kb cDNAs showed that two of the three viruses had a genomic organization similar to that of other Sapporo-like strains and the third strain (London/92) lacked an open reading frame overlapping the 5' end of the capsid gene. Alignment of the capsid sequences of these three strains showed 44-78% amino acid identity among the three strains. Phylogenetic analysis of the aligned sequences indicated the three strains are related but each belongs to a distinct genetic cluster. The genetic differences are associated with antigenic differences in that an enzyme immune assay (EIA) specific for the prototype Sapporo/82 strain detected the Houston/86 strain, but not the Houston/90 and London/92 strains. In vitro transcription and translation of viral cDNA containing the predicted capsid gene of Houston/90 resulted in a protein of 63 K, which is immunoprecipitated by sera from children infected with the strain. Genetically and antigenically distinct strains in the Sapporo-like HuCVs have not been described previously and the occurrence of such diverse strains in the same community likely increases the importance of these strains as a cause of illness in children.