Serologic markers, HLA-DQ2 haplotype, and clinical features suggestive of celiac disease were studied to assess their diagnostic value in a multicentric study to detect celiac disease in 675 first-degree relatives of 227 celiac probands. Serum IgA-class anti-endomysium and IgA-class anti-gliadin antibodies were positive in 5.8% and 1.9% of relatives, respectively. HLA-DQ2 haplotype was present in 64% of relatives, and the overall rate of celiac disease diagnosed by intestinal biopsy was 5.5%. The frequency of HLA-DQ2 in the celiac patients and controls was 93% and 18%, respectively. The most frequent clinical features--diarrhea, anemia, food intolerance, and growth retardation--were not present in one third of the celiac disease relatives. We conclude that the assessment of IgA-class anti-endomysium antibodies alone seems a reasonable approach for screening celiac disease in relatives and cannot be replaced by an accurate clinical anamnesis. HLA-DQ2 haplotype may identify the population with a high genetic susceptibility to celiac disease.