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Histamine stimulates acid secretion by the parietal cell and this secretion is inhibited by the histamine H2-receptor antagonists. Whole body autoradiography showed that radioactivity from 14C-histamine was localized in the artery walls of the stomach and in the muscularis mucosae, but that the level in the fundic mucosa was the same as the blood. When the H2-receptor antagonists burimamide, metiamide and cimetidine were labelled with 35S, 14C or 3H and dosed to rats, whole body autoradiography showed that the stomach was predominantly labelled in the glandular mucosa from 5 to 120 min after administration. Microautoradiography in the rat and dog after intravenous injection of [3H]metiamide or [3H]cimetidine demonstrated an uptake of tritium in the parietal cell cytoplasm that was 3- to 4-times greater than that found in adjacent peptic cells or areas of muscularis mucosa. The preferential labelling persisted at a low level up to 6h after injection in the rat. The localization of radioactivity from the H2-antagonists in the parietal cell cytoplasm correlates well with their pharmacological activity in preventing acid secretion from this cell.