We compared the diagnostic accuracy of a new immunological marker of celiac sprue (CS), the antijejunum antibody (JAB), with that of antigliadin (AGA) and antiendomysium (EmA) antibodies. One hundred untreated adults with biopsy-proven CS, 52 healthy controls, and 57 patients with inflammatory bowel disease, lymphoma of the small bowel, Whipple's disease, and irritable bowel syndrome were investigated. Only JAB and EmA were detected at a similar titer in all patients with untreated CS but in no controls (100% sensitivity and specificity). Sensitivity of AGA was, respectively, 55% for IgA and 78% for Ig class, with a 100 and 82% specificity. The differences in frequencies between both EmA and JAB with IgA and IgG AGA were highly significant. We conclude that JAB and EmA provide a reliable noninvasive screening test for clinically significant gluten-sensitive enteropathy. The lower cost of IgA-JAB is a major advantage, owing to the different availability of the lower third of the esophagus and jejunum from primates. The sensitivity and specificity of the two tests are almost identical, but we find interpreting EmA easier than JAB especially when the titer is low.