1. The antagonism at alpha-adrenoceptors by thymoxamine and phentolamine of the response to noradrenaline was investigated in the limb veins and arteries of man.2. Brachial artery infusions of thymoxamine (40 mug/min) produced rises in resting arterial flow of up to 100%. When infused mixed with noradrenaline, thymoxamine (40 mug/min) attenuated the blood flow response to noradrenaline. Blockade was of a similar degree to that which occurred following a 10 min infusion of phentolamine (40 mug/min).3. Local intravenous infusion of thymoxamine (400-2,000 ng/min) mixed with noradrenaline attenuated the venoconstrictor response to noradrenaline. The degree of attenuation was similar to that seen after a 10 min infusion of phentolamine (500 ng/min). Blockade after thymoxamine did not last longer than 16 minutes. Neither thymoxamine nor phentolamine altered resting venous compliance.4. Local intravenous infusions of thymoxamine (500 ng/min) and phentolamine (500 ng/min) abolished the sympathetically mediated venoconstriction produced by overbreathing.5. Systemic injection of thymoxamine (0.1 mg/kg) did not block the reduction in forearm arterial flow produced by locally infused noradrenaline. In two out of three experiments, however, it produced some antagonism of noradrenaline induced venoconstriction. Systemic phentolamine (5 mg) blocked the effect of noradrenaline in the arterial bed, but antagonized its actions in the veins in only one out of three experiments.