A household survey in 1991, at the onset of the Latin American cholera epidemic, investigated high attack rates in Trujillo, Peru, and determined the association between blood group 0 and severe cholera. Of 463 persons in 69 households, 173 (37%) reported diarrhea, 21% required rehydration therapy, and 4% were hospitalized; these treatment requirements greatly exceeded estimates based on other populations. Elevated vibriocidal or antitoxic antibody titers were present in 52% of 321 from whom serum was obtained; 73% were blood group O. Blood group 0 was strongly associated with severe cholera: Infected persons had more diarrheal stools per day than persons of other blood groups, were more likely to report vomiting and muscle cramps, and were almost eight times more likely to require hospital treatment. Since prevalence of blood group 0 in Latin America may be the world's highest, estimates of treatment requirements should be increased to prevent unnecessary deaths.