Effects of intracerebroventricular (i.c.v.) administration of endothelin-3 (ET-3) on renal sympathetic nerve activity (RSNA) and renal blood flow (RBF), arterial blood pressure and heart rate were examined in conscious rats. Administration of ET-3 (1-50 pmol) through a chronically implanted cannula evoked an increase in arterial blood pressure and decreases in heart rate and RSNA, whereas RBF measured by Doppler flow probes did not change. Maximum changes in these responses occurred 10-15 min after i.c.v. administration of ET-3 and the responses returned to the control level after approximately 60 min. In sinoaortic denervated (SAD) rats, the decrease in RSNA induced by i.c.v. ET-3 was attenuated but still significantly persistent. During the experiments, we found that the injection of ET-3 (50-100 pmol) induced a barrel rotation, with an onset latency of 10-15 min. In those cases, prominent increases in arterial blood pressure and RSNA were observed, and these lasted for more than 60 min. The result shows that ET-3 can have centrally mediated effects on autonomic nerve activity as well as on cardiovascular function.