Celiac disease, a common chronic gastrointestinal disorder, is gluten induced and is controlled with a gluten-free diet. While the management of CD with a gluten-free diet is quite effective, the diagnosis is rather difficult. The ESPGAN criteria for the diagnosis of CD seems to be tedious and time-consuming. Serological tests for IgA class endomysial antibodies, as detected by indirect immunofluorescence, on human and primate smooth muscles are specific and sensitive markers of celiac disease. Of all the specimens examined, endomysial antibodies were present in patients with gluten-sensitive enteropathy. These antibodies occurred in all active cases of celiac disease, in 90 percent suspected celiac patients where all the ESPGAN criteria has not been fulfilled. This contrasts to the presence of endomysial antibodies in 46 percent of confirmed and 17 percent of suspected celiac patients maintained on a gluten-free diet for various time intervals. Endomysial antibodies also occurred in all cases with chronic diarrhea and gut histology consistent with CD and 8% of asymptomatic family members of CD patients. None of the patients with other gastrointestinal and liver diseases had endomysial antibodies. These studies thus emphasize the specificity and sensitivity of endomysial antibodies for celiac disease.