Pancreatic polypeptide (PP) and peptide YY (PYY) are released by the gut in response to nutrients and inhibit food intake in rodents and humans. We hypothesized that PP and PYY(3-36) would inhibit feeding additively. Fasted male C57BL/6 mice were injected intraperitoneally with saline, PP, PYY(3-36) or PP+PYY(3-36) (n=7-10). Food intake at 1 h was significantly inhibited by 6 nmol kg(-1) PP and by 6 nmol kg(-1) PYY(3-36) (P<0.05) but not significantly following 3 nmol kg(-1) PP+3 nmol kg(-1) PYY(3-36). In a higher dose study 30 nmol kg(-1) PP, 30 nmol kg(-1) PYY(3-36) and 30 nmol kg(-1) PP+30 nmol kg(-1) PYY(3-36) all inhibited 1 h food intake compared with saline (P<0.05) but there was no significant difference in the food intake of the combined group compared with either hormone individually. Subsequently, 16 fasted lean healthy human volunteers (6 men and 10 women) received, in random order, 90 min intravenous infusions of saline, 4 pmol kg(-1)min(-1) PP, 0.4 pmol kg(-1)min(-1) PYY(3-36) and 4 pmol kg(-1)min(-1) PP+0.4 pmol kg(-1)min(-1) PYY(3-36). A pasta lunch was served 60 min following infusion. There was no evidence of a greater decrease in food intake with the combined PP+PYY(3-36) treatment (buffet meal energy intake (KJ): saline 2633+/-204, PP+PYY 2693+/-254, PP 2367+/-199, PYY 2511+/-196). These results suggest that PP and PYY(3-36) do not inhibit feeding additively in rodents or humans.