Chromogranin A (CgA) is an acidic protein co-released with catecholamines during exocytosis from sympathetic nerve terminals and chromaffin cells. Previous work has demonstrated that large scale perturbations in sympathetic nervous system (SNS) functioning result in corresponding changes in CgA levels in plasma. Little is known about the physiologic significance of CgA. We hypothesized that, since CgA and catecholamines are co-released from the same storage vesicles, and since CgA is not subject to reuptake or enzymatic metabolism, plasma CgA should reflect norepinephrine release from sympathetic terminals. We therefore measured venous CgA, norepinephrine levels, and norepinephrine release rate in 30 unmedicated subjects. Although the correlation of CgA with plasma norepinephrine was only modest (r = 0.37, p less than 0.05), its correlation with norepinephrine release rate was highly significant (r = 0.58, p less than 0.001). Thus, CgA may offer a novel perspective on peripheral sympathetic activity.