Chromogranin A is the major catecholamine storage vesicle soluble protein costored and coreleased by exocytosis with catecholamines. Immunoreactive chromogranin A circulates in human plasma, where it may reflect changes in exocytotic sympathoadrenal activity. We measured plasma chromogranin A concentration in normotensive control subjects as well as in untreated essential (primary) hypertensive subjects and subjects with several varieties of secondary hypertension. Plasma chromogranin A concentration was higher in subjects with essential hypertension (n = 32) than in normal controls (n = 18; 198 +/- 32 versus 129 +/- 12 ng/ml [mean +/- SEM]; p less than 0.05), and was also elevated in subjects with hypertension secondary to renal parenchymal disease (n = 9; 192 +/- 36 ng/ml; 0.05 less than p less than 0.1) and those with pheochromocytoma (n = 11; 1614 +/- 408 ng/ml; p less than 0.01). In essential hypertensive subjects (n = 5), short-term suppression of sympathetic outflow with oral guanabenz (4 mg) reduced plasma chromogranin A concentration within 30 to 60 minutes, while the blood pressure response was more gradual and was maximal at 3 hours. The results suggest that plasma chromogranin A is, at least in part, under neural control and that there may be an excess of exocytotic sympathoadrenal activity in essential hypertension. These initial studies are now being expanded to larger subject groups.