Gluten-sensitive enteropathy is characterized by flattening of intestinal villi and malabsorption caused by the toxic effect of gluten, a wheat protein. Gluten activates an endogenous mechanism of toxicity that may be the local mucosal immune system: local mucosal immunoglobulin and antigluten antibody production occur soon after gluten ingestion. Approximately 80% of patients with this disease possess HL-A8, a second segregant series antigen. This association also occurs in dermatitis herpetiformis, a disease with vesicular skin lesions and gluten-sensitive flattening of intestinal villi. The association suggests that the fundamental abnormality in enteropathy is a binding reaction involving gluten protein and a binding site on a cell surface, determined in part by the histocompatibility gene; this reaction then results in a local mucosal immune response to gluten. Alternatively, the fundamental abnormality may be the presence of an abnormal immune-response gene linked to the HL-A8 gene or acting in concert with it; this immune-response gene results in local mucosal production of antigluten antibody.