One hundred seventy-two patients requiring upper gastrointestinal tract endoscopy were examined prospectively for evidence of herpes simplex virus type 1 (HSV-1) infection. No viruses were recovered from active ulcers (11 with duodenal and eight with gastric ulcers). Using both enzyme-linked immunosorbent assay (ELISA) and standard complement fixation methods, patients with endoscopically proved active duodenal ulcer had significantly higher mean serum antibody levels to HSV-1 (but not to cytomegalovirus) than those without evidence of peptic ulcer. Neither patients with a history of or evidence of past peptic ulcer nor those with active gastric ulcer had higher serum antibody levels to HSV-1 compared with subjects without ulcers. These data provide support for an association between active duodenal ulcer and HSV-1 infection, the nature of which is not defined by these studies.

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