Background: Celiprolol, a newer beta-blocking agent, has been reported to have vasodilatory capacity which may be due to partial beta-2-receptor agonistic activity or to alpha-receptor antagonistic or central sympathoinhibitory effects. Methods: To more critically assess the physiologic effects of celiprolol, we measured sympathetic nerve activity to muscle (MSNA), forearm blood flow (FBF), blood pressure (BP), central venous pressure, and heart rate (HR) in 10 normal volunteers at rest, during unloading of cardiopulmonary baroreceptors with lower body negative pressure (LBNP), and during a cold pressor test (CPT). Responses were compared with those seen with metoprolol and with placebo, i.e. each subject was studied three times. Results: Celiprolol did not alter resting levels of hemodynamics, FBF, and MSNA nor did it alter responses to LBNP or the CPT. In contrast, metoprolol produced significant decreases of FBF and HR, and increases of forearm vascular resistance and BP, but had also no effect on responses to the applied stress tests. Conclusions: The lack of peripheral vasoconstriction seen after acute administration of celiprolol is most likely due to its partial beta-2-receptor agonistic effect and does not seem to be due to a central or reflex action or to an alpha-blocking effect. Both beta-blockers do not impair fundamental neural mechanisms involved in circulatory homeostasis.