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We evaluated the sensitivity and kinetics of serum IgA class anti-endomysial antibodies in the diagnosis of celiac disease (CD) as established by the criteria of the European Society for Pediatric Gastroenterology and Nutrition (ESPGAN). Eighty-four cases that satisfied the ESPGAN criteria for CD were evaluated for IgA-EmA titers during various phases of establishing the diagnosis. Thirty-three cases were infants and children <5 years of age undergoing intestinal biopsies for symptoms of CD and 51 were previously diagnosed adults. Of the 33 children, 11 were untreated and symptomatic and were IgA-EmA positive at initial presentation. Twenty-two children previously controlled on a gluten-free diet (GFD) exhibited IgA-EmA titers during gluten challenge. Furthermore, the antibody levels declined in all cases (usually to negative) when the patients were again placed on a GFD for 6–12 months. Changes in intestinal histopathology paralleled the changes in antibody tilers in six cases undergoing serial biopsies. Of the 51 adult patients with proven CD who were prescribed a GFD for at least 12 monlhs, IgA-EmA were detected in 10 cases who were noncompliant to their GFD, whereas the antibodies was found in only 1 of the remaining 41 patients striclly adhering to their diet. The sera of 140 aged-matched children wilh various inleslinal problems, 87 healthy adults, and 67 patients with dermatological diseases served as controls and were also IgA-EmA negative. On the basis of these findings, we suggest a role for the IgA-EmA as a serological screening test for active CD. It further offers the potential for monitoring compliance to diet in established cases of CD and also indicates the proper timing for biopsy in patients undergoing evaluation of CD.