Origanum compactum has been studied for antispasmodic activity, using different smooth muscle preparations of the alimentary canal in vitro: the guinea-pig ileum and duodenum, the rat fundus strip and duodenum. Aqueous extract of Origanum powder inhibits responses to acetylcholine, histamine, Serotonine, BaCl2, 1,1-dimethyl-4-phenylpiperazinium iodide and nicotine in the guinea-pig ileum. The extract also blocks contractions elicited by electrical coaxial stimulation. Responses to cumulative increased Ca2+ concentrations in depolarizing bathing medium were also blocked. Thymol and carvacrol were found to be the active components. The results indicate that antispasmodic activity is caused by a direct and indirect action on the smooth muscle. It is suggested that muscle relaxant effect results from a decrease of the Ca2+ availability for muscle contraction by I) blocking the release of intracellular bound Ca2+ and 2) prevention of the extracellular Ca2+ influx in the smooth muscle cell. Inhibition of the nerve action potential in the postganglionic nerve fibre is proposed to be the indirect action of spasmolytic activity.