Acidification of the duodenum of healthy young subjects with 40 mEq of acid during 1 h resulted in a 45-percent inhibition of acid output in response to 0.15 μg/kg/h of pentagastrin, but had no effect on acid output stimulated with 6.0 μg/kg/h of pentagastrin. There was no significant effect of duodenal acidification on the total output of pepsin. Since secretin stimulates pepsin secretion, endogenous secretin alone cannot account for the inhibition of acid secretion. Duodenal acidification with the subjects own gastric acid had no significant effect on gastric secretion. The physiological significance of the effects described seems, therefore, uncertain.