A panel of documented arthritogenic Shigella flexneri strains as well as an epidemic-associated non-arthritogenic Shigella sonnei control was used to identify a 2-megadalton plasmid specific to the arthritogenic strains. The plasmid, pHS-2, contains a DNA sequence that encodes a 22-amino acid polypeptide encompassing a pentapeptide homologous to part of the polymorphic region of the alpha-1 domain of HLA-B27. These results suggest that molecular mimicry between arthritogenic bacterial-encoded epitopes and the HLA-B27 molecule may play a role in the development of reactive arthritis.