Two series of experiments were performed in anesthetized dogs to test the hypothesis that the suppression of renin secretion by clonidine results from a centrally mediated decrease in the activity in the renal sympathetic nerves. In the first series, clonidine (1 mug/kg) was administered directly into the third ventricle of a group of dogs in which renal perfusion pressure was controlled by adjusting an aortic clamp. In these animals, clonidine produced hypotension and bradycardia and suppressed plasma renin activity to 39 percent of the control value. These changes in blood pressure and plasma renin activity were closely correlated. Intraventricular clonidine produced similar alterations in blood pressure and heart rate in another group of dogs in which renal perfusion pressure was not controlled, but failed to suppress plasma renin activity. In the second series of experiments, clonidine was administered intravenously in a dose of 30 mug/kg. Intravenous clonidine produced a transient hypertension followed by hypotension, decreased heart rate and suppressed plasma renin activity to 49 percent of the control value. Renal denervation reduced renin secretion and prevented the suppression of renin secretion produced by intravenous clonidine. Thus, these data are consistent with the hypothesis that the suppression of renin secretion by clonidine results from a centrally mediated decrease in renal sympathetic neural tone. This suppression may be overcome by large falls in renal perfusion pressure.