To evaluate the determinants of the plasma norepinephrine (NE) response to orthostatic stress, NE kinetics were measured during steady-state infusion of [3H]NE of high-specific activity for two consecutive 90-minute periods; the first was supine, and the second was during 60 degrees head-up tilt. In 6 normal subjects, plasma NE increased from 242 to 570 pg/ml, and NE clearance decreased from 1.43 to 1.00 l/min X M2. In 6 patients with congestive heart failure, there was no significant change in plasma NE during orthostatic stress. This has been interpreted previously to indicate that there was little activation of the baroreflex arc. In fact, NE clearance decreased from 1.08 to 0.79 l/min X M2; however, there was a decrease in NE spillover from 4.04 to 2.88 nmol/min X M2. A reduction of organ blood flow with tilt could be responsible for the reduced NE clearance by both groups, but the mechanism for the reduction in NE spillover with tilt in congestive heart failure is unclear.