A tissue preparation is described which makes it possible to examine the effect of drugs on the nerves that control both longitudinal and circular muscles of the small intestine. The preparation consists of a segment of rat ileum set up to measure the tension developed in the longitudinal muscle and intraluminal pressure developed by the circular muscle in response to transmural electrical stimulation. The method showed that both muscles differed in their patterns of responses to transmural stimulation from the threshold of 2.5-60 Hz. All responses were tetrodotoxin-sensitive, the fast longitudinal muscle contraction and the intraluminal pressure response being caused by both pre- and postganglionic cholinergic nerves. The responses differed in their sensitivities to the alpha 2-adrenoceptor agonists clonidine and UK 14,304, whereby the cholinergic responses of the circular but not longitudinal muscle were inhibited by the agonists. Comparison of results with the guinea-pig ileum set up in the same way revealed a marked species variation in responses, in that the intraluminal pressure response of the guinea-pig ileum was not sensitive to alpha 2-adrenoceptor agonists. This clear species difference makes it possible to use the circular muscle of the rat ileum, as measured indirectly via intraluminal pressure, to assess compounds for activity at alpha 2-adrenoceptors over a wide range of frequencies.