The intestinal perfusion technique was used in 10 healthy subjects to measure the effects of pentagastrin (PG) on jejunal and ileal net and unidirectional movements from two isotonic solutions, one of which was glucose-free (solution I) and the other contained 30 mM glucose (solution II); in five further subjects, the effect of the pentapeptide on intrajejunal transit time was assessed, (a) In the jejunum, PG had no effect on net movements of water and electrolytes from solution I, whereas it significantly reduced net absorption of water, sodium, potassium and chloride from solution II, without affecting the absorption of glucose itself, (b) Both jejunal unidirectional fluxes of water, sodium and potassium were reduced by pentagastrin, whatever the solution infused; but, in the presence of glucose, the insorption (lumen to blood flux) of water and electrolytes was predominantly decreased, (c) PG did not modify intrajejunal transit time of fluid, (d) Ileal transport of water and ions was not affected by PG. The mechanism of the action of PG is discussed in the light of current knowledge of transport mechanisms across the intestine, and the possibility is raised that it may act through a reduction of the size of the ‘pores’ of the plasma membrane of the enterocyte. Finally, it is suggested that overproduction of gastrin, as seen in the Zollinger-Ellison syndrome, may play a direct role in the watery diarrhea sometimes observed in this disease.