A method of establishing chronic gastric fistulae in rats is described. In rats with chronic gastric fistulae, the basal acid output was 48.8 +/- 2.9 microEq/100 g/hr and the basal pepsin output was 543 +/- 28 micrograms tyrosine/100 g/hr. The effects of urethane-induced anesthesia, pyloric ligation, and acute laparotomy on gastric secretion in rats were examined. Both urethane-induced anesthesia and acute laparotomy depressed gastric secretions. In Ghosh-Schild rats, the basal acid output was 3.2 +/- 0.4 microEq/100 g/hr and the basal pepsin output was 70 +/- 13 micrograms tyrosine/100 g/hr. The persistent and very low level of of gastric secretion in these animals appears to result from the combination of both urethane anesthesia and invasive surgery. Because the rats with chronic gastric fistulae do not require anesthesia, invasive surgery, or pyloric ligation, which may play very important roles in the regulation of gastric functions, this kind of preparation is a suitable method for studying the physiology and pharmacology of gastric secretions in the rat.