Diminution of antisecretory effect of H2-receptor antagonists with repeated oral dosing, termed tolerance, has been established in healthy volunteers. Anecdotal evidence indicates the development of tolerance with intravenous dosing. These findings demonstrate that tolerance may be clinically relevant in diseases where tight control of acidity is required. Patients with duodenal ulcer disease, however, do not develop significant tolerance, according to the sparse investigations available. Tolerance will, at most, only be of minor clinical significance in failures of DU to heal. The mechanisms implicated in the development of tolerance remain unclear.