Neuropeptide Y (NPY) is thought to be co-released with catecholamines in response to major cardiovascular stresses, but its relation to the release of catecholamines in response to minor stresses has been less well described. We therefore studied the response of plasma NPY-like immunoreactivity (NPY-Li) levels to standing (10 min) in eight normal subjects and 11 patients with congestive heart failure, and to short-term (6 h) vasodilator therapy in 13 patients with congestive heart failure. In both normal and heart failure patients, NPY-Li decreased (296±73 to 233±63 pg.ml⁻¹ and 652±36 to 516±25 pg.ml⁻¹ (P <0.01) respectively) in response to standing, whereas catecholamines increased in both groups (norepi-nephrine 203±73 to 507± 165 pg.ml⁻¹ and 493±197 to 813±336 pg. ml⁻¹ (P<0001) respectively and epinephrine 23±12 to 38±12 pg.ml and 46±19 to 62±28 pg.ml⁻¹ (P <0.001 respectively). Both basal circulating NPY-Li and catecholamine levels were markedly increased in congestive heart failure patients, but catecholamines and NPY-Li did not correlate with each other. After 6 h of nitroglycerin infusion, mean arterial pressure was decreased, but circulating neurohumoral levels remained unchanged and NPY-Li levels decreased (653±37 to 517±26 pg.ml⁻¹ P<0.01). It is concluded that basal circulating NPY-Li and catecholamine levels are increased in congestive heart failure and that this neurohormone could play a concomittant role in the increase in peripheral resistance in these patients. However, changes in circulating NPY-Li levels correlate poorly with changes in circulating catecholamines in response to minor cardiovascular stress in normal and heart failure patients. These results suggest a differential release of these two sympathetic neurotransmitters.