Clonidine and methyldopa lower blood pressure in animals by an action on the central nervous system. The hypotensive action of oral clonidine (300 pg) in man also appears to be centrally mediated as the hypotensive action was abolished in tetraplegic subjects with post-traumatic cervical spinal cord transection. Similar results in rabbits indicate the importance of the integrity of bulbospinal sympathetic outflow. The integrity of afferent baroreceptor fibres was not essential for the hypotensive action in man or rabbits. Plasma noradrenaline, as an index of sympathetic activity, was reduced after single doses and chronic treatment with clonidine in normotensives and hypertensives. The beta blocker, propranolol (200 mg orally), lowered blood pressure in normotensive men by a small but significant amount. Plasma noradrenaline changes were much less prominent than following clonidine. Hypertensive patients on chronic oral treatment with propranolol alone did not have significantly different plasma levels of noradrenaline t o patients on diuretics or those on no treatment. Although clonidine appears to exert its hypotensive action via the central nervous system, we have not established that the major site of propranolol's effect is on efferent sympathetic outflow.