Cholera is a waterborne diarrheal disease that continues to plague the developing world. Individuals become infected by consuming water from reservoirs contaminated by virulent strains of the bacterium Vibrio cholerae. Epidemiological and environmental observations of a cholera outbreak in Dhaka, Bangladesh, suggest that lytic bacteriophage specific for V. cholerae may limit the severity of cholera outbreaks by killing bacteria present in the reservoir and in infected individuals. To quantify this idea and generate testable hypotheses, we analyzed a mathematical model that combines the epidemiology of cholera with the population dynamics of the bacteria and phage. Under biologically reasonable conditions, we found that vibriophage can ameliorate cholera outbreaks. If phage predation limits bacterial density before an outbreak, a transient reduction in phage density can disrupt that limitation, and subsequent bacterial growth can initiate a cholera outbreak. The severity of the outbreak depends on the density of phage remaining in the reservoir. If the outbreak is initiated instead by a rise in bacterial density, the introduction of phage can reduce the severity of the outbreak and promote its decline. In both situations, the magnitude of the phage effect depends mainly on vibrio growth and phage mortality rates; the lower the rates, the greater the effect. Our analysis also suggests that either bacteria in the environmental reservoir are hyperinfectious or most victims ingest bacteria amplified in food or drinking water contaminated by environmental water carrying few viable V. cholerae. Our theoretical results make a number of empirically testable predictions.Vibrio cholerae ͉ epidemiology C holera, a waterborne gastroenteric infection, remains a significant threat to public health in the developing world. The disease in its severest form causes copious diarrhea lasting from 3 to 7 days. Death from dehydration is typical in the absence of treatment. Pathogenic serotypes of the bacterium Vibrio cholerae, expressing cholera toxin encoded by a lysogenic bacteriophage (1), are responsible for the majority of cases. V. cholerae and other members of this bacterial genus naturally colonize lakes, rivers, and estuaries (2, 3); local outbreaks are precipitated and prolonged by contamination of local water supplies in areas of poor sanitation. Disease transmission usually occurs through ingestion of contaminated water or feces rather than through casual human-human contact.Outbreaks of cholera occur cyclically, usually twice per year in endemic areas, and the intensity of these outbreaks varies over longer periods. Extrinsic factors, such as large-scale weather cycles (e.g., the El Niño-Southern Oscillation), and intrinsic factors such as postinfection immune periods have been shown to correlate in time with components of the epidemic cycle (4-6). Recently, Faruque et al. (7) proposed that lytic bacteriophage predation on pathogenic vibrio may be an important extrinsic factor influencing the epidemic cycle on short time...