We examined the effects of clonidine injected unilaterally into the rostral ventrolateral medulla (RVLM) of conscious, unrestrained rats. We also examined whether the local alpha(2)-adrenoceptor mechanism contributed to the action of clonidine injected into the RVLM. Injection of clonidine but not vehicle solution significantly decreased the mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) in conscious, unrestrained rats as well as in propofol-anesthetized rats. The frequency of natural behavior was significantly lower after clonidine injection than after vehicle injection. The depressor and sympathoinhibitory responses were significantly larger in the propofol-anesthetized rats than in the conscious rats. Coinjection of a selective alpha(2)-adrenoceptor antagonist, 2-methoxyidazoxan, with clonidine into the RVLM significantly attenuated the depressor, bradycardiac, sympathoinhibitory, and sedative effects of clonidine injected alone. In conclusion, clonidine injected into the RVLM decreased MAP, HR, and RSNA and caused sedation in conscious, unrestrained rats. The action of clonidine in the RVLM was at least partly mediated by alpha(2)-adrenoceptor mechanisms.