1 Inflammatory diseases of the pancreas or diseases which cause obstruction within the biliary or pancreatic duct system are associated with severe pain. Although neuropeptides such as substance P are present in the biliary tree, only few capsaicin-sensitive, substance P-positive nerve fibres have been found in the ducts. In order to obtain functional evidence whether capsaicin-sensitive afferent neurones transmit nociceptive information arising from the biliopancreatic duct, blood pressure reflexes following electrical stimulation of the duct or increases in intraductal pressure were determined in barbiturateanaesthetized rats.2 Electrical stimulation of neurones in the biliopancreatic duct was carried out at 30 V, 3 ms, 50 Hz for 20 s. In untreated animals the electrical stimulation resulted in rises in blood pressure by up to 25 mmHg, but in about a quarter of all animals tested this response was absent. Following the administration of phentolamine (7 pmol kg-', i.p.) the blood pressure responses were changed to pronounced and reproducible depressor reflexes of -5 to -30 mmHg. Retrograde injections into the biliopancreatic duct of 300 g1 of a 154 mm sodium chloride solution produced increases in intraductal pressure of approximately 1O mmHg. This elicited shortlasting falls in blood pressure of 3-15 mmHg. Phentolamine significantly augmented the fall in blood pressure to 8-30 mmHg. 3 The depressor reflexes observed in both models after the administration of phentolamine were abolished by morphine (1 gmol kg-', i.v.). The inhibition by morphine was reversed by naloxone (3 pmol kg-, i.v.). Naloxone given before morphine did not affect the depressor reflex but prevented the inhibitory action of subsequently injected morphine. 4 Acute s.c. injection of capsaicin (30 mg kg-') abolished the depressor reflexes in response to both types of nociceptive stimulation in phentolamine-treated rats. The initial pressor effects of electrical stimulation were only partly inhibited by capsaicin whereas the basal depressor reflexes in response to elevation of intraductal pressure were abolished. In rats which had received capsaicin on the day before the experiment or had been treated with capsaicin as neonates, only minor rises in blood pressure were induced by electrical stimulation at the beginning of the experiment and no changes in blood pressure occurred after the administration of phentolamine. After adult or neonatal pretreatment with capsaicin the depressor reflexes in response to increased intraductal pressure were only small and were unchanged by phentolamine. 5 The depressor reflexes following either electrical stimulation or increases in intraductal pressure were abolished by the unselective P-blocker, (-)-propranolol (3 gtmol kg-', i.p.), and greatly reduced by the PI-blocker, metoprolol (6 ;Lmol kg-', i.p.). The P2-preferring adrenoceptor antagonist, butoxamine (3 ,umol kg-', i.p.), had no effect on the depressor responses. The reflex falls in blood pressure were also abolished by hexamethonium (10 pmol kg-', i.p...