Transmural electrical stimulation of the sympathetic nerve endings of human saphenous vein biopsies released two forms of NPY identified chromatographically as native and oxidized peptide. The release process is dependent on extracellular calcium, the frequency, and the duration of the stimuli. While guanethidine reduced the overflow of ir-NPY, phenoxybenzamine did not augment NPY release, but increased that of noradrenaline. Oxidized NPY, like native NPY, potentiated the noradrenaline and adenosine 5'-triphospahate-induced vasoconstriction, an effect blocked by BIBP 3226 and consonant with the RT-PCR detection of the mRNA encoding the NPY Y1 receptor. These results highlight the functional role of NPY in human vascular sympathetic reflexes.