To determine risk factors for cholera in an epidemic-disease area in South America, a case–control investigation was performed in Guayaquil, Ecuador, in July 1991. Residents > 5 years old who were hospitalized for treatment of acute, watery diarrhoea and two matched controls for each were interviewed regarding sources of water and food, and eating, drinking, and hygienic habits. Interviewers inspected homes of case-patients and controls to document water treatment, food-handling, and hygienic practices. Faecal specimens and shellfish were cultured for Vibrio cholerae O 1. Isolates were tested for susceptibility to a variety of antimicrobial agents. Drinking unboiled water (odds ratio [OR] = 4.0, confidence interval [CI] = 1.8–7.5), drinking a beverage from a street vendor (OR = 2.8, CI = 1.3–5.9), eating raw seafood (OR = 3.4, CI = 1.4–11.5), and eating cooked crab (OR = 5.1, CI = 1.4–19.2) were associated with illness. Always boiling drinking water at home (OR = 0.5, CI = 0.2–0.9) was protective against illness. The presence of soap in either the kitchen (OR = 0.3, CI = 0.2–0.8) or bathroom (OR = 0.4, CI = 0.2–0.9) at home was also protective. V. cholerae O 1 was recovered from a pooled sample of a bivalve mollusc and from 68% of stool samples from case-patients. Thirty-six percent of the isolates from stool specimens were resistant to multiple antimicrobial agents. Specific prevention measures may prevent transmission through these vehicles in the future. The appearance of antimicrobial resistance suggests the need for changes in current methods of prevention and treatment.