The new epidemic strain O139 of Vibrio cholerae, the etiologic agent of cholera, has probably emerged from the pandemic strain O1 E1 Tor through a genetic rearrangement involving the horizontal transfer of exogenous O-antigen- and capsule-encoding genes of unknown origin. In V. cholerae O139, these genes are associated with an insertion sequence designated IS1358O139. In this work, we studied the distribution of seven genes flanking the IS1358O139 element in 13 serovars of V. cholerae strains. All these O139 genes and an IS1358 element designated IS1358O22-1 were only found in V. cholerae O22 with a similar genetic organization. Sequence analysis of a 4.5-kb fragment containing IS1358O22-1 and the adjacent genes revealed that these genes are highly homologous to those of V. cholerae O139. These results suggest that strains of V. cholerae O22 from the environment might have been the source of the exogenous DNA resulting in the emergence of the new epidemic strain O139.