To study interactions between intraluminal acid and protein digests, six dogs with chronic gastric and pancreatic fistulas received three sets of intestinal perfusates. The first set contained HCl (1, 2, or 4 mmol/50 ml) and 64 mM D- or L-phenylalanine. The second set contained HCl plus either intact or pepsin-digested bovine serum albumin (BSA); the BSA and HCl were varied so that each 50 ml contained 1, 2, or 4 meq of acid titratable from an initial pH of 2.0 to an end-point pH of 4.5. The third set was identical to the second set except for an initial pH of 3.5. All perfusates were adjusted to 300 mosM and randomly infused at 200 ml/h. L-Phenylalanine enhanced acid-induced bicarbonate and protein outputs, as did pH 2.0 BSA digests. At pH 3.5, only acid-induced protein output was augmented by BSA digests. In additional studies, undigested or digested BSA at pH 7.0 was infused with secretin (82 pmol.kg-1.h-1). Only digested BSA enhanced secretin-induced pancreatic secretion. We conclude that there is an important, albeit complex, interaction between the intestinal acid stimulus and the protein digest stimulus on pancreatic secretion.