The effects of acute administration of two antihypertensive drugs, clonidine and propranolol, on plasma NPY and catecholamine levels were compared in sinoaortic denervated (a model associated with a marked increase in sympathetic tone and a rise in blood pressure) and normal conscious dogs. Clonidine decreased plasma noradrenaline and NPY concentrations in both groups of animals. Propranolol failed to change plasma noradrenaline and NPY levels in sinoaortic denervated dogs but elicited a decrease in plasma noradrenaline with no change in NPY levels in normotensive animals. The present experiments show that changes in plasma noradrenaline and NPY concentrations are not always simultaneous. The decrease in plasma NPY concentrations could contribute to the sympatholytic effect of clonidine.