The reported increase of gastric secretion after small bowel (SB) resection is controversial. To determine the effect of SB resection on gastric acid secretion we studied basal and dose step pentagastrin-stimulated gastric acid secretion as well as basal serum gastrin, secretin, neurotensin and postprandial gastrin levels in 12 dogs, before and after resection of 60% of the intestine representing both proximal (n = 6) and distal (n = 6) SB. Rat bioassay was also performed to rule out the presence of unknown gastric secretagogues in the blood. Proximal SB resection produced a significant increase in basal and low dose (100 ng/kg/h) pentagastrin-stimulated gastric acid secretion (ED50 = 1,110 vs. 720 ng/kg/h after resection). However, no significant changes in gastric secretion were observed after distal SB resections. Neither proximal nor distal SB resection altered basal or postprandial serum gastrin levels. Proximal SB resection reduced serum secretin levels (229 +/- 38 vs. 134 +/- 16 pg/ml, p < 0.05) but did not alter neurotensin levels. Rat bioassay failed to reveal a circulating secretagogue after SB resections. We conclude that proximal but not distal SB resection increases basal and submaximally stimulated gastric acid secretion. Such an effect may be due to the observed decrease in circulating secretin levels.