Using hydrogen gas clearance technique to measure gastric mucosal blood flow (GMBF) and a high dose of capsaicin to ablate the capsaicin-sensitive afferent neurons, the role of capsaicin-sensitive neurons in the gastric acid secretion and hyperemic response to intragastric peptone was investigated. The results were as follows: (1) there was an increase in acid secretion associated with the hyperemic response to intragastric peptone; (2) pretreatment with a high dose of capsaicin to ablate afferent neurons completely abolished the gastric hyperemic response to intragastric peptone and partially inhibited the acid secretion; (3) the gastric hyperemic response to intragastric peptone was completely blocked by pretreatment with L-nitro-arginine methyl ester (L-NAME), whereas the acid secretion was significantly attenuated; (4) inhibited effects of L-NAME on acid secretion and GMBF could be reversed by pretreatment with L-arginine (L-ARG); (5) pretreatment with atropine inhibited gastric acid output (GAO) and partially attenuated GMBF. These results suggested that capsaicin-sensitive afferent neurons and endogenous NO were involved in the gastric acid secretion and hyperemic response to intragastric peptone and the hyperemic response was mediated by both cholinergic and noncholinergic neurons.