OBJECTIVES: Recent studies suggest that celiac disease was previously underdiagnosed. To find out whether antien-domysial antibodies underestimate the prevalence of celiac disease, we elected to use a strategy combining multiple serological markers to explore the prevalence of celiac disease in Israel and the usefulness of the various antibodies in screening for celiac disease. METHODS: Serum samples from 1571 healthy blood donors were tested. A small intestinal biopsy was offered to all patients who tested positive for either human tissue transglutaminase antibodies, an ELISA kit based on antiendomysium (EMA-ELISA), immunoglobulin A antigliadin verified by antiendomysial immunofluorescence antibodies, and to patients who were IgA deficient with elevated antigliadin IgG. RESULTS: A total of 59 subjects (3.8% of study population) were offered an intestinal biopsy based on serological findings, and 30 of 59 patients agreed to undergo intestinal biopsy (1.9% of study population), Celiac disease was diagnosed in 10 patients, establishing a prevalence of at least 1:157 in the general population (0.6%, CI = 0.3-1.1%). Using any serological marker alone would have underestimated the prevalence of celiac disease, as it was diagnosed in only two patients who tested positive for endomysial immunofluorescence antibodies (prevalence of 1:786, 0.1%, CI = 0.02-0.5%), six patients positive for tissue transglutaminase (prevalence of 1:262, 0.4%, CI = 0.1-0.9%), and seven patients positive for ELISA-EMA (prevalence of 1:224, 0.45%, CI = 0.2-0.9%). CONCLUSIONS: The prevalence of celiac disease in Israel is at least 1:157 in the general population, confirming its underdiagnosis in previous studies. The disparity between the various serological markers suggest that the use of one serological marker is insufficient for establishing the true prevalence of celiac disease.