The effects of pancreatic intraductal infusions of the surface active pancreatic ductogram enhancing agent, polyoxyethylene hydrogenated castor oil, were studied in the dog. Moderately high pressure retrograde infusions of 5 per cent polyoxyethylene hydrogenated castor oil into the main pancreatic duct resulted in pancreatitis-like changes significantly greater than those seen in the saline solution control group. These changes persisted despite buffering of the agent to physiologic pH and the elimination of nonphysiologically high pressure by direct ductal perfusion. Similar inflammatory changes were associated with ductal perfusion using oleic and, to a lesser degree, ricinoleic-fatty acids at concentrations of 10(-4) molar sufficient to account for the titratable acidity of 5 per cent polyoxyethylene hydrogenated castor oil. It is postulated that residual-free fatty acids may play some role in polyoxyethylene hydrogenated castor oil related toxicity. The surface active properties of the agent may also be involved. Caution and further research are recommended prior to widespread use of the agent in endoscopic retrograde pancreatography.