Methysergide (1 and 3 mg/kg i.v.) caused dose-dependent reductions in blood pressure and heart rate of anesthetized cats. In addition, sympathetic nerve discharges of the postganglionic renal nerve were also markedly reduced by the same doses of drug. Pressor responses to electrical stimulation of the diencephalon were inhibited by 3 mg/kg but not 1 mg/kg of methysergide. These results suggest that methysergide acts to decrease blood pressure by a centrally mediated reduction in sympathetic nervous outflow and, at higher doses, can additionally prevent pressor changes caused by electrical activation of suprabulbar central structures. These results are in agreement with previous reports that methysergide has little or no peripheral effects on the cardiovascular system.