We report two cases of duodenal ulcer (DU) identified at endoscopy in a pair of dizygotic twins; their outstanding clinically recognizable features were a very early onset, a great familiar occurrence, a lack of triggering conditions (drugs, burns, stress, sepsis, respiratory distress), normal serum levels of gastrin and pepsinogen I, inadequate response to medical treatment with H2-receptor antagonists, but satisfactory response to associated therapy with H2-receptor antagonists and sucralfate. Results of this study show that examined twins were affected by a form of early-onset primary DU, probably inherited like an autosomal dominant disorder with high degree of penetrance, associated with normal serum pepsinogen I and gastrin; in this form of Du a decreased tissue resistance of duodenal mucosa is likely more important, pathogenically, than an increased peptic secretion. At present long-term prognosis of our patients is unknown.