S erotonin and substance P of gastrointestinal origin have been measured by radioimmunoassay in the bowel lumen under basal and stimulated conditions. To investigate the possibility that local blood flow may be influenced by these endoluminal hormones, 26 cats were studied with exogenous serotonin and substance P infused endoluminally into isolated proximal jejunal segments in vivo. Regional blood flow was measured by using the radioactive microsphere technique before, during, and after the endoluminal instillation of two doses of substance P (3.9 and 30 ng/min) or serotonin (0.9 and 21 micrograms/min). Neither dose of substance P changed systemic blood pressure. Substance P at the low dose caused an increase in blood flow to the experimental jejunal mucosa (from 53 +/- 10 ml/min per 100 g to 102 +/- 20 ml/min per 100 g, P less than 0.01). The higher dose of endoluminal substance P similarly increased blood flow to the experimental jejunal mucosal fraction, and also increased blood flow to the experimental jejunal muscularis fraction (from 17 +/- 3 ml/min per 100 g to 23 +/- 3 ml/min per 100 g, P less than 0.02). Serotonin increased blood flow to the experimental jejunal muscularis only at the high dose (17 +/- 4 ml/min per 100 g to 25 +/- 4 ml/min per 100 g tissue, P less than 0.01). These results provide evidence for a dose-related local effect of endoluminal substance P on gastrointestinal blood flow.