Fludrocortisone depressed plasma norepinephrine in normal subjects but to a lesser degree than it depressed renin activity or urinary aldosterone excretion. Sympathetic nervous reactivity (defined as upright/supine plasma norepinephrine) was decreased more than supine plasma norepinephrine. Pretreatment supine plasma norepinephrine (but not plasma renin activity or aldosterone excretion) correlated with blood pressure changes during fludrocortisone dosing, which suggests participation of the sympathetic nervous system in the blood pressure elevations reported during exogenous steroid administration or primary aldosteronism. Suppression of sympathetic nervous activity and reactivity by fludrocortisone tends to explain its limited usefulness in patients with autonomic dysfunction and postural hypotension.