Metiamide has been found to be about 10 times more active than burimamide in vitro in antagonizing histamine H2-receptors and nearly 5 times more active in vivo as an antagonist of histamine or pentagastrin-stimulated secretion. Effective oral ED50 doses for inhibition have been estimated as 25 μmole kg−1 against basal secretion in rats and 16 μmole kg−1 against maximal histamine-stimulated secretion in dogs. Administration of metiamide orally daily for 90 days with doses of 1,500 μmole kg−1 to rats and 700 μmole kg−1 to dogs produced signs of kidney damage as the dominant lesion in both species. These toxic doses are roughly 60 and 44 times greater than the ED50 doses in the rat and dog, respectively. These results show that metiamide has the degree of activity and safety needed for a compound to be a candidate for through clinical evaluation.