Urapidil is an antihypertensive agent known to have central 5HT1A agonistic properties in addition to alpha-1 blocking effects. To assess the importance of these effects, we compared the hemodynamic effects of a single oral dose of urapidil (U, 60 mg) with those of prazosin (Pr, 2 mg), clonidine (Cl, 0.15 mg), and placebo (Pl), at rest, during orthostatic tilt, and during submaximal graded bicycle exercise tests, in a double-blind randomised crossover study in 24 healthy male volunteers. The variables studied were heart rate, mean blood pressure, cardiac index by bioimpedance, systemic vascular resistance index (SVRI), and plasma norepinephrine. Baseline values before drug administration were identical. At rest, during tilt, and during identical exercise, compared to placebo, urapidil and prazosin caused similar decreases in SVRI, with a smaller increase in HR after urapidil than after prazosin (p < 0.01), and without any difference in BP. Both drugs increased norepinephrine in a similar manner. In contrast, clonidine decreased blood pressure (p < 0.01) and norepinephrine (p < 0.01) with no difference in heart rate or SVRI. In conclusion, at rest, during tilt and during exercise, urapidil and prazosin have similar vasodilating effects, but the sympathetic stimulation is less and the parasympathetic stimulation greater after urapidil than after prazosin, probably indicating a centrally acting effect of urapidil. However, the sympathoinhibitory effect of urapidil is less marked than that of clonidine.