This is a study of the injurious effects of transient reflux of diverse solutions when introduced into the pancreas of rats under pressure through the obstructed duodenum. Mild pan Immune complex disease creatitis resulted from introduction of saline. Administration of homologous or heterologous proteinaceous solutions induced moderate pancreatitis; prior sensitization of the animals to the respective protein did not aggravate the inflammatory process. Severe pancreatitis developed after intraduodenal injection of nephrotoxic serum (basement membrane antibodies) or preformed immune complexes. It is suggested that pancreatitis ensues as a result of reflux of solutions carrying activators of trypsinogen from the duodenum into the ducts at a time when pancreatic secretion is enhanced by intestinal hormones. Pancreatic damage results from passage of the activated enzymes across the acinar and ductular epithelium into the interstitial tissue. The severity of the pancreatitis is augmented when immune mechanisms are superimposed. An attempt at demonstrating organ-specific antigens in the urine of rats with pancreatitis was unsuccessful.