Vibrio cholerae, the causative agent of cholera, requires two coordinately regulated factors for full virulence : cholera toxin (CT), a patent enterotoxin, and toxin-coregulated pill (TCP), surface organelles required for intestinal colonization. The structural genes for CT are shown here to be encoded by a filamentous bacteriophage (designated CTX Phi), which is related to coliphage M13. The CTX Phi genome chromosomally integrated or replicated as a plasmid, CTX Phi used TCP as its receptor and infected V. cholerae cells within the gastrointestinal tracts of mice more efficiently than under laboratory conditions, Thus, the emergence of toxigenic V. cholerae involves horizontal gene transfer that may depend on in vivo gene expression.