To test the hypothesis that vascular pain depends on sympathetic drive under physiological conditions we studied the effects of both alpha-adrenoceptor stimulation by noradrenaline and alpha-adrenoceptor blockade by phentolamine on the intensity of physicochemically evoked pain from veins in humans. In seven healthy volunteers, a vascularly isolated hand vein segment was perfused continuously with noradrenaline (6 x 10(-9)-6 x 10(-6) M), or phentolamine (1.24 x 10(-4) M). Pain was evoked by intraluminal electrostimulation or by injection of hyperosmolar saline during control perfusion of isoosmolar saline and after each noradrenaline concentration, as well as after perfusion of phentolamine. Subjects rated pain intensity continuously on an electronically controlled visual analogue scale (VAS) between 0% VAS (no pain) and 100% VAS (tolerance maximum). Intravenous electrostimulation as well as hyperosmolar solutions evoked pain in each subject. The intensity of pain was neither influenced by noradrenaline, nor by phentolamine, so that nociception from blood vessels is unlikely to be modulated by the sympathetic nervous system under physiological conditions in humans.