Trypanosoma cruzi is the protozoan parasite that causes American trypanosomiasis (Chagas' disease). Chagas' disease is endemic in Latin America. The infection is usually seen in poor people who live in rural areas in substandard housing, where they are bitten by infected reduviid bugs. Transmission also can occur by blood transfusion. Infected individuals who immigrate to the United States might donate blood if they are asymptomatic and unaware of their infection. This study evaluated the usefulness of a questionnaire for identifying T. cruzi-infected individuals among prospective blood donors who met all American Association of Blood Banks, Food and Drug Administration, and State of California criteria for donor eligibility. Seventy-two of 3492 otherwise eligible donors were disqualified because of their answers on the questionnaire. Forty-five of these 72 agreed to be tested serologically, and 2 were positive for T. cruzi antibodies. One of six autologous blood donors tested also was positive for T. cruzi antibodies. We conclude that the questionnaire selected a subgroup of Latin Americans at high risk for T. cruzi infection. The deferral of these high-risk individuals clearly reduced the risk of transmission of T. cruzi by transfusion, without intolerably decreasing the supply of donated blood.