Neuropeptide Y (NPY) coexists with noradrenaline in postganglionic sympathetic neurons and with noradrenaline and adrenaline in the central nervous system. The possibility that NPY is released into the circulation during activation of the sympathoadrenal system was investigated in ten moderately hypertensive volunteers using three different stimuli. In healthy moderately hypertensive volunteers cold pressor test, head up tilt and graded bicycle exercise resulted in increased blood pressure, heart rate and plasma catecholamine concentrations. While there was a trend for plasma NPY-like immunoreactivity (NPY-LI) to increase during cold pressor test and head up tilt, NPY-LI concentration only increased significantly during bicycle exercise, the stimulus of greatest duration. These results suggest that plasma NPY-LI can be released into the circulation on sympathoadrenal activation in moderately hypertensive subjects and demonstrate that the pattern of release is similar to that previously observed in normotensive subjects.