The mechanism of vasodepressor reaction induced by head-up tilt test in patients with vasodepressor syncope is not clearly understood. We hypothesized that an abnormal alteration of beta-adrenergic transmission could be involved in these patients. We measured plasma catecholamine concentration during tilt and density of beta-adrenoceptors and tested the effects of beta-adrenergic blockers in the prevention of the vasodepressor reaction in patients with vasodepressor syncope. Ten patients had reproducibly induced vasodepressor syncope (mean 3.1 +/- 0.3 episodes in each patient) with head-up tilt (80 degrees) for 10 minutes with isoproterenol infusion (1 to 3 micrograms/min). Syncope occurred at 6.3 +/- 1.7 minutes during tilt with isoproterenol infusion. The plasma norepinephrine concentration before administration of beta-blocker was significantly elevated during tilt compared to the supine position (0.347 +/- 0.079 ng/ml in supine position with isoproterenol vs 0.468 +/- 0.082 ng/ml at 3 minutes of tilt, p < 0.001, and vs 0.503 +/- 0.106 ng/ml at the onset of vasodepressor reaction, p < 0.005; n = 8). Plasma norepinephrine after administration of the selective beta 1-adrenergic blocker metoprolol (40 mg/day) was similarly elevated (0.282 +/- 0.071 ng/ml in supine position with isoproterenol vs 0.390 +/- 0.078 ng/ml at 3 minutes of tilt, p < 0.05, n = 6; and vs 0.547 +/- 0.152 ng/ml at the onset of vasodepressor reaction, p < 0.001, n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)