To investigate whether peptide YY (PYY) has a role in minimising fluid loss during diarrhoea, its effect on hypersecretion induced by vasoactive intestinal peptide (VIP) was studied in seven subjects with ileostomies. An isotonic electrolyte solution containing polyethylene glycol 4000 was infused directly into the duodenum and the effluent was collected for 40 min (baseline), then VIP was infused intravenously at 5 pmol.kg-1.min-1 for 500 min. PYY was infused intravenously at low doses (0.4 and 0.2 pmol.kg-1.min-1) for 100 min each during the continuous VIP infusion. Small-intestinal secretion was assessed by effluent weight and by polyethylene glycol dilution, which gave similar results. Plateau ileal output was 501 (SEM 33) ml/h during VIP infusion. PYY caused significant falls in secretion--to 404 (48) ml/h for the lower dose and to 323 (75) ml/h for the higher. It also prolonged small-bowel transit. These findings suggest that PYY is a natural inhibitor of diarrhoea and that its therapeutic potential merits investigation.