To examine hemodynamic, plasma catecholamines, and cyclic AMP changes during tilt in patients with neurocardiogenic (vasodepressor) syncope, six patients underwent 80 degrees head-up tilt test for 10 minutes with isoproterenol infusion (1-3 micrograms/min). Venous blood was sampled in the supine position, at 3 minutes of tilt, and at the onset of vasodepressor reaction during tilt. All patients had previous tilt studies in which vasodepressor syncope had been induced reproducibly (mean 3.3 episodes in each patient). Syncope was induced at 6.1 +/- 0.4 minutes of tilt with an infusion of isoproterenol (mean 1.7 +/- 0.3 micrograms/min). Although arterial pressure and heart rate did not change significantly between in the supine position and at 3 minutes of tilt, plasma norepinephrine increased significantly at 3 minutes of tilt (0.44 +/- 0.10 ng/mL; P < 0.05) and at the onset of vasodepressor reaction (0.49 +/- 0.12 ng/mL; P < 0.01) compared to the supine position with isoproterenol (0.34 +/- 0.10 ng/mL). Also, cyclic AMP (cAMP) increased significantly at 3 minutes of tilt (25.3 +/- 2.0 pmol/mL; P < 0.005) and at the onset of vasodepressor reaction (29.6 +/- 1.7 pmol/mL; P < 0.005) compared to the supine position with isoproterenol (20.4 +/- 1.9 pmol/mL). After administration of selective beta 1-blocker, metoprolol (40 mg/day), plasma norepinephrine, and cAMP during tilt did not change significantly compared to baseline tilt. However, metoprolol prevented the syncope in 3 of 6 patients. After administration of beta 1-, beta 2-blocker, propranolol (30 mg/day), cAMP at 3 minutes of tilt decreased significantly compared to the baseline tilt (16.9 +/- 1.4 pmol/mL vs 25.3 +/- 2.0 pmol/mL; P < 0.05) and propranolol prevented the syncope in all six patients. We concluded that the increase of cAMP may play an important role for the induction of vasodepressor reaction in patients with neurocardiogenic (vasodepressor) syncope. The concentration of cAMP showed more sensitive response to vasodepressor reaction than that of norepinephrine.