Clonidine, an imidazoline derivative, is a widely used antihypertensive agent which acts by stimulating the alpha 2-adrenergic receptors at the central nervous system. Clonidine also seems to exert beneficial effects on baroreceptor reflex sensitivity which is usually altered by arterial systemic hypertension and arteriosclerosis. Aim of the study was to compare acute and chronic hypotensive response and the effects on baroreflex sensitivity of a newly synthesized central alpha 2-adrenergic agonist, guanfacine, with those induced by clonidine. The effects of acute and chronic treatment were studied by evaluating blood pressure modifications through intraarterial or sphygmomanometric detection. Baroreflex sensitivity was studied before and after acute treatment with the two drugs. Our results show that guanfacine and clonidine may induce comparable effects, both reducing arterial blood pressure levels and heart rate with an order of potency for guanfacine 10 times lower than clonidine. After chronic treatment the effect of guanfacine on blood pressure was more pronounced than that observed after clonidine administration. Both drugs may enhance baroreflex sensitivity, with a more evident effect of guanfacine than clonidine in response to a sudden decrease of blood pressure. This suggests that guanfacine could afford a more effective cardiovascular adaptation during acute hypotension (i.e. during orthostatic hypotension), particularly in the elderly hypertensive patients.