The possibilities of participation of adenosine in the peristaltic reflex of guinea pig ileum was studied pharmacologically and histologically. Adenosine apparently depressed the peristaltic activity induced by elevation of intraluminal pressure from zero to 1-8 cm H2O, and the extent of the depression somewhat decreased in proportion to the elevation in intraluminal pressure. Also, dipyridamole depressed the peristaltic activity by itself; however, the extent of the depression significantly increased in proportion to the elevation in intraluminal pressure. On the other hand, in the presence of dipyridamole, the elevation of the intraluminal pressure from zero to 1-8 cm H2O elicited an 3H-output increase from 3H-adenosine preloaded guinea pig isolated ileum, with the effect being more pronounced as the pressure was increased. In contrast, the peristaltic activity was more pronounced at lower pressurization. Atropine greatly depressed the peristaltic response but did not affect 3H-output induced by 4 cm H2O pressurization. Tetrodotoxin depressed both markedly. Fluorescence histochemical localization of quinacrine, which binds to adenosin triphosphate (ATP), revealed dense nerve cell bodies and fine interconnecting strands in the ileal myenteric plexus of Auerbach. Also, in microradioautographs of ileal longitudinal muscle incubated with 3H-adenosine, the concentration of developed silver grains was localized in the ganglion cells and in the musculature as varicose fibre. From these results, evidence is provided that the peristalsis of guinea pig ileum may be physiologically modulated by endogenous adenosine, which may be released from neuronal elements of the myenteric plexus in response to the applied intraluminal pressure.