This study sought to understand the pathogenesis of hemorrhagic abomasitis in calves by characterizing a type A Clostridium perfringens isolate. The complete genome sequence of an isolate from an outbreak of hemorrhagic abomasitis was compared to the three complete C. perfringens genomes currently available in GenBank. Unique findings included the presence of an integrated plasmid sequence and a frameshift mutation in the virS gene, which encodes the main sensor kinase that controls virulence gene regulation. An ~ 55 kb plasmid similar to pCW3 was found, in addition to two smaller plasmids with no significant similarity to available C. perfringens plasmid sequences. A number of plasmid-related fragments were also identified. Neither genomic nor proteomic approaches identified novel toxins, but an alternate and unexpected picture of virulence has emerged suggesting that anomalous virulence gene regulation might contribute to pathogenicity in this isolate. / Natural Sciences and Engineering Research Council, the Ontario Graduate Scholarship, the Animal Health Strategic Initiative of the Ontario Ministry of Agriculture, Food and Rural Affairs