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Background: Recent epidemiologic studies in Europe using antigliadin (AGA) and anti-endomysium antibodies (AEA) for initial screening have shown that the overall prevalence of celiac disease (CD) is about 1:300. There are no comparable scientific data for the USA, where CD is considered rare. The main aim of this study was to determine the prevalence of increased AEA in healthy blood donors in the USA., Methods: Sera from 2000 healthy blood donors were screened for IgG AGA and IgA AGA with an enzyme-linked immunosorbent assay test. All those with increased AGA levels, those with intermediate levels, and random samples with low levels were tested for AEA, using both monkey esophagus (ME) and human umbilical cord (HUC) cryosections as substrates., Results: The mean age of the blood donors was 39 years, with 52% being men, 85.2% being Caucasian, 11.8% African-American, 1.5% Asian, and 1.5% Hispanic. Eight healthy blood donors had positive AEA tests on both monkey esophagus and human umbilical cord. Among the eight subjects with increased AEA levels seven were Caucasian and one was African-American. All the four examined AEA-positive donors carried the known susceptibility alleles for CD., Conclusions: The prevalence of increased AEA levels in healthy blood donors in the USA is 1:250 (8:2000). This is similar to that reported in countries in Europe, where subsequent small-intestinal biopsies have confirmed CD in all those with AEA positivity. On the basis of a high positive predictive value of the AEA antibody test, it is likely that the eight blood donors identified in this study have CD. These data suggest that CD is not rare in the USA and that there is need for a large-scale epidemiologic study to determine the precise prevalence of the disease in the USA.