Transfusion-associated Chagas' disease is a serious public health problem in Central and South America. With the recent influx of immigrants from Chagas' disease-endemic areas, concern about the risk of disease from blood transfusion has increased in the United States. To assess the prevalence of Trypanosoma cruzi infection in one area, 1024 consecutive blood donations from 988 voluntary blood donors at a medical center in Los Angeles County were screened serologically. The median age of donors screened was 32.5 years; 53.4 percent were male, and 38.4 percent were born in Chagas' disease-endemic countries. All donor sera were tested by complement fixation (CF) and indirect immunofluorescence (IIF) tests. A radioimmunoprecipitation assay (RIPA) was also done on all sera from CF- or IIF-reactive donors and an equal number of sera from nonreactive donors. A second serum specimen was obtained, and interviews were completed for 18 (67%) of 27 donors with an initial CF titer greater than or equal to 8 or an IIF titer greater than or equal to 64. The overall seroreactivity (by CF and IIF) was 1.1 percent (11/988). One donor (0.1%) had antibody specific to the 72- and 90-kDa antigens of T. cruzi on RIPA. Seven recipients of blood components from the seroreactive donors were located and were seronegative at 3 to 6 months. Seroreactive donors were 3.6 times more likely to have been born or to have resided in Mexico or Central America, 8.7 times more likely to have donated blood in the past, and 11.8 times more likely to have a history of malaria prophylaxis or treatment.