Background: Dermatitis herpetiformis (DH) is a cutaneous manifestation of gluten-sensitive enteropathy (celiac disease). Patients with DH demonstrate circulating IgA antibodies against epidermal transglutaminase (eTG) and tissue transglutaminase (tTG). It has been suggested that eTG is the autoantigen of DH. Objective: The purpose of this study was to characterize the autoimmune response to eTG and tTG in patients with DH on a normal or gluten-free diet (GFD). Methods: Sera from 52 patients with DH were studied for the presence of IgA antibodies to eTG and tTG by enzyme-linked immunosorbant assay. In 38 patients, serum was obtained before initiation of a GFD, whereas 14 patients had been on a GFD for at least 2 years. Results: Autoantibodies against eTG were detected in 36 of 38 patients (95%) and those against tTG in 30 of 38 patients (79%) with DH on a normal diet. Of 14 patients on a long-term GFD, 7 patients were free of DH lesions and did not require dapsone treatment. None of these patients showed circulating antibodies against eTG or tTG. The remaining 7 patients on a GFD were not able to stop taking dapsone. All these patients demonstrated anti-eTG antibodies, whereas only 3 of them showed additional reactivity against tTG. Limitation: Autoantibody levels against eTG and tTG before and after introduction of a GFD were not examined in the same patients. Conclusion: Our data suggest that antibodies to eTG are the most sensitive serologic marker in treated and untreated patients with DH and confirm the central role of eTG in the pathogenesis of this disease. (J Am Acad Dermatol 2009;61:39-43.).