This study evaluated the possibility that the endothelial cells of microscopic lymphatic vessels can release vasoactive agents which affect the lymphatic vessels and nearby arterioles. Microinotophoresis of acetylcholine (ACh) or bradykinin (BK) onto the wall of quiescent submucosal lymphatic vessels in the rat small intestine had no discernible effects on their diameters but caused spontaneously active mesenteric lymphatic vessels to constrict. Application of ACh or BK to the arteriolar wall caused significant vasodilation. Release of either drug onto the wall of a nearby lymphatic produced arteriolar dilation that was approximately 80% of that observed with direct application to the arteriolar wall; drug application into parenchymal tissue produced a dilation less than 25% of that observed during application to the lymphatic. NG-monomethyl-L-arginine application to the lymphatic blocked all ACh-induced lymphatic-mediated responses but had no effect on the response to direct ACh application to the arteriolar wall or any of the responses to BK application. These results are consistent with the hypothesis that lymphatic endothelial cells are capable of releasing agents that dilate nearby arterioles and cause spontaneously active lymphatic vessels to constrict.