In an attempt to clarify the role of the sympathetic neurone in the antihypertensive action of propranolol, the effect of this drug on responses to lumbar sympathetic nerve stimulation has been studied in the perfused hind-limb of the dog. 2. No consistent reduction of maximal or submaximal responses to nerve stimulation was produced by propranolol (10 to 100 mug/kg). In contrast, potentiation of nerve-evoked response, as well as those to injected noradrenaline, usually occurred. Dexpropranolol (50 mug/kg) had no effect. 3. When neuronal uptake of noradrenaline was inhibited by desmethylimipramine or cacaine, no reduction in responses to sympathetic nerve stimulation was observed with propranolol. 4. No evidence was found, using alpha-adrenoceptor blocking drugs, that released transmitter stimulates beta-adrenoceptors in the blood vessels of the hind-limb. 5. No evidence has been found for the existence of an adrenergic neurone-blocking action of propranolol that might contribute to the antihypertensive activity in man.
