The effect of histamine on Mg-ATPase was assessed in homogenates of gastric biopsies taken from the body and antrum of the stomach of patients with and without duodenal ulcer (DU). Histamine at concentrations greater than 10(-7) mol/l caused significant activation of this crude enzyme activity in the body mucosa from both groups of patients; maximum stimulation of enzyme activity was greater in the DU patients than in the non-DU group. No activation by histamine was found in ATPase of antral biopsies. Administration of cimetidine (1 g/day orally) to DU patients for 28 days abolished the histamine activation of the enzyme activity. Investigation of the activity of enzymes in normal biopsies showed that the effect of histamine was not shared by the specific H2 agonist, impromidine, or H1 agonist, 2-(2-aminoethyl)-thiazole, and that cimetidine inhibition of ATPase in vitro is probably not an histamine-receptor-specific effect.