The stimulation of pepsinogen secretion by the presence of topical acid has previously been demonstrated in the dog (by a locally mediated, cholinergic mechanism) and suggested in man. The current experiments quantified the effect of luminal acid on pepsin secretion in man by using gastric instillations of acid solutions and recoveries with gastric washes. Solutions tested (pH 0.84-5.0) included buffered solutions, hydrochloric and acetic acid solutions, and an aspirin-acid solution. Decreasing pH or increasing acid concentration led to a significant increase in pepsin output, with a mean maximum increase of 70% over basal (pH 5.0) at the lowest pH (pH 0.84). The secretion of pepsin as a result of similar concentrations of hydrochloric or acetic acid did not differ, nor was pepsin secretion augmented by aspirin, used as a 'barrier breaker', and it was not related to calculated duodenal delivery of acid. Thus, any in vivo study of pepsin secretion should be interpreted in the light of the possible stimulatory contribution of acid.