Patients with duodenal ulcer have lowergastroduodenal mucosal histamine and a reduced tissuefibrinolysis at the ulcer edge. In the duodenal mucosafibrinolysis is regulated by the tissue-type andurokinase-type plasminogen activators; and inhibitors type 1and type 2. Trends across ordered groups leading frommucosa of nonulcer control subjects,“normal” mucosa of ulcer patients, to ulceredge were found in tissue-type plasminogen activatorconcentration, histamine concentration, and histaminemethyltransferase activity. Concentrations oftissue-type activator, inhibitor type 1, and histaminewere significantly lower at ulcer edge than at normal. An inversecorrelation was found between histaminemethyltransferase and plasminogen activator activities,methyltransferase and tissue-type activator, andmethyltransferase and histamine. These results support thehypothesis that in active ulceration, reduction intissue fibrinolytic activity is closely associated withenhanced release and metabolism of histamine.