Dermatitis herpetiformis (DH) is highly associated with celiac disease. Recently, tissue transglutaminase (tTG) was identified as the autoantigen of IgA antibodies in celiac disease. The prevalence of antibodies to tTG in DH patients is not known. The purpose of this study was to determine whether DH patients show circulating IgA autoantibodies to tTG, to compare their serum levels with those from patients with other subepidermal autoimmune bullous diseases, and to correlate levels of antibodies to tTG with the extent of small bowel disease. Sera were obtained from consecutive patients with DH (n = 11), linear IgA disease (n = 15), bullous pemphigoid (n = 10), and epidermolysis bullosa acquisita (n = 6) and were studied by indirect immunofluorescence on monkey esophagus and NaCl-split human skin. IgA reactivity to tTG was measured by enzyme-linked immunosorbent assay. The extent of mucosal involvement in jejunal biopsy specimens was assessed according to the grading of Marsh. All untreated DH patients showed circulating IgA autoantibodies to tTG. One DH patient already undergoing therapy, the 15 patients with linear IgA disease, and all other controls revealed no autoantibodies to tTG. In addition, serum levels of IgA anti-tTG antibodies reflected the degree of histopathologic changes in jejunal mucosa from biopsy specimens in DH patients. Our results show that circulating IgA autoantibodies to tTG are detectable in DH but not in linear IgA disease or other subepidermal autoimmune bullous diseases. The levels of IgA anti-tTG antibodies reflect the extent of histopathologic changes of the jejunal mucosa in DH.