In October 1992, a non-Ol strain of Vibrio cholerae emerged as a cause of epidemic cholera in India and Bangladesh. This antigenically novel clone has been designated serogroup 0139 synonym Bengal. Since its emergence, V. cholerae 0139 has caused a massive cholera epidemic throughout and beyond the Indian subcontinent. Molecular analysis of virulence determinants in clinical isolates suggests that 0139 strains are highly related to El Tor 01 strains. Unlike other non-O 1 strains, 0139 strains carry multiple copies of the cholera toxin genetic element and also genes for the toxin-coregulated pilus. These results guided construction of a live V. cholerae 0139 vaccine prototype through deletion of genes for at least four specific virulence determinants (ctxA, ace, zot, and cep) as well as other factors involved in site-specific and homologous recombination (RS1, attRS1, and recA). It is hoped that this attenuated live vaccine will help control the pandemic spread of V. cholerae 0139.