To study the functional role of the recently found leucine 7 to proline 7 (Leu7Pro) polymorphism in the signal peptide of preproneuropeptide Y, sympathetic responses, including neuropeptide Y (NPY) release, were compared during strenuous physical exercise between subjects with the Leu7/Pro7 genotype and their matched wild-type controls (Leu7/Leu7 genotype). To further evaluate the effect of this polymorphism on the intracellular processing of preproNPY, isolated human umbilical vein endothelial cells (HUVEC) of corresponding genotypes were compared using immunocytochemical methods to verify the presence and localization of NPY and proNPY in these cells by confocal microscopy.