Both experimental cholecystitis and luminal distension inhibit fluid absorption and stimulate motor activity in the gall bladder. These functional alterations are mimicked by exogenous prostaglandins (PGs) and inhibited by potent cyclooxygenase inhibitors, but direct evidence of a primary role of endogenous PGs is not available. Therefore, experiments in the cat were carried out in which the effects of lyso-phosphatidylcholine (lysoPC; 0.5-2.0 mmol/l), implantation of cholesterol stones, and raised intraluminal pressure in the gall bladder lumen were assessed. The gall bladder was perfused in vivo at a constant rate by a buffer solution. PGE2 was determined in the effluent by a radioimmunological method validated by gas chromatography-mass spectrometry. PGE2 output was markedly (p less than 0.01) raised (13.9 +/- 2.6 vs 1.1 +/- 0.5 ng/h; n = 10) during lysoPC perfusions and this response was inhibited by 66% (p less than 0.02) after indomethacin administration (2 mg/kg iv). A significant (p less than 0.05) increase in PGE2 output occurred six weeks after implantation of gall stones (3.7 +/- 1.5 ng/h; n = 6) and in response to distension of the normal gall bladder wall (3.6 +/- 1.2 ng/h; n = 6). These findings support the theory that PGs play an important pathophysiologic role in biliary tract disease.