Anti-endomysial autoantibodies are very useful in the diagnosis and monitoring of celiac disease (gluten-sensitive enteropathy) due to their high sensitivity and specificity for that disorder. The recent discovery that the autoantigen responsible for the endomysial pattern is tissue transglutaminase (tTG) has led to the commercial development of automated enzyme immunoassays for quantitation of that autoantibody. These assays are standardized to provide highly accurate and comparable testing between laboratories for anti-tTG autoantibodies. Celiac disease is a common genetic disease in populations of Europe and the United States. It has a spectrum of expression ranging from silent or mild to severe, with resulting malabsorption that produces multiple-organ system effects due to malnutrition. Many cases miss the diagnosis because the symptoms are not classic or the clinical syndrome is not severe. Because the treatment of celiac disease (avoidance of wheat products) is so effective and inexpensive and because celiac disease is so common in selective populations, a highly reliable test for its detection such as anti-tTG should find wide application in clinical practice.