Neuropeptide Y (NPY), a 36-amino-acid peptide, was measured in the peripheral circulation and ileal lumen of conscious dogs using a sensitive radioimmunoassay. Fasting NPY concentrations averaged 448 +/- 15 pg/ml in the peripheral blood and 364 +/- 23 pg/ml in the ileal effluent. Following a mixed meal, circulating NPY levels rose to 499 +/- 37 pg/ml (P less than 0.05), whereas recoverable quantities of ileal intraluminal NPY fell to 257 +/- 19 pg/ml (P less than 0.05). Neither fat nor glucose meals significantly changed circulating or ileal intraluminal NPY recovery. These results demonstrate release of NPY into the blood and ileal lumen for the first time and support NPY as a candidate gut hormone.