The role of the enteric nervous system of the gallbladder on mucosal water absorption was evaluated by intraluminal administration of capsaicin, a selective stimulant of afferent nerve endings. It has been postulated that the neural responses of the gallbladder are peptidergic and mediated by prostanoids. Anesthetized cats underwent gallbladder perfusion with a physiological buffer solution containing I4C polyethylene glycol as a nonabsorbable tracer to quantitate mucosal water absorption. Capsaicin was added to the perfusate and administered intraluminally at a rate of 5 mg/kg-I/hr-l for 2 hr. One experiment on five cats was performed when capsaicin was administered and five control experiments were performed when only vehicle was added to the perfusate. Five experiments were performed when indomethacin was administered intravenously (5 mg/kg-'/hr-') and buffer solution alone was used to perfuse the gallbladder, and five experiments were performed when capsaicin was added to the perfusate and indomethacin was administered intravenously. Additional experiments were performed when lidocaine was added to the perfusate and when lidocaine and capsaicin were administered simultaneously. Gallbladder absorption and perfusate and tissue prostaglandin E and 6 keto prostaglandin F,_ concentrations were evaluated. To determine whether capsaicin induced gallbladder inflammation, tissue myeloperoxidase concentrations were measured. Control feline gallbladders absorbed approximately 0.6 mlhr. Indomethacin alone significantly decreased gallbladder absorption. Capsaicin administration increased gallbladder absorption to approximately 1.6 ml/hr, and this increase was significantly inhibited by indomethacin. Lidocaine significantly decreased control, and capsaicin stimulated gallbladder absorption. Capsaicin significantly increased perfusate prostaglandin E and 6 keto prostaglandin F,_ concentrations with significant depletion of tissue prostanoids. Indomethacin significantly decreased perfusate prostanoid concentrations while decreasing the water absorption during capsaicin administration, suggesting that the two processes are related. Lidocaine eliminated the increased perfusate prostaglandin E concentrations produced by capsaicin but did not alter the increased concentrations of 6 keto