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Previous studies of cholera transmission have been conducted in the middle or at the end of an epidemic. Since modes of transmission could be different in different phases of an epidemic, we initiated a case-referent study immediately after the first cases had been hospitalized in a recent cholera epidemic in Guinea-Bissau in West Africa in October 1994. The cases investigated were consecutive adult patients resident in the capital of Bissau who were admitted the the National Hospital during the first two weeks of the epidemic. Referents were matched for district, gender, and age. The study showed a protective effect of using limes in the main meal (odds ratio [OR] = 0.2, 95% confidence interval [CI] = 0.1–0.3) and having soap in the house (OR = 0.3, 95% CI = 0.1–0.8). Not eating with the fingers and using water from a public standpipe were also protective. No specific source or mode of transmission was identified. Thus, cholera control programs in Africa may have to emphasize general hygienic conditions and the use of acidifiers in food preparation.