The present study explored the impact of pharmacological blood pressure elevation on cortical activation and reaction time in chronic hypotension. Effects of the sympathomimetic etilefrine were investigated in 50 hypotensive persons based on a randomized, placebo-controlled double blind design. As an indicator of cortical excitability, the contingent negative variation (CNV), induced by a constant foreperiod reaction time task, was assessed at frontal (F3, Fz, F4) and central (C3, Cz, C4) scalp sites. Etilefrine provoked a decrease in the frontal and central CNV. In contrast, shorter reaction times were observed following drug administration. The degree of pharmacologically induced blood pressure elevation was correlated to CNV attrition as well as to performance enhancement. Inhibitory effects of baroreceptor activation on cortical excitability and enhanced cerebral blood flow are considered to be involved in mediating the effects of blood pressure elevation on cerebral functioning. Implications for the treatment of chronic hypotension are discussed.