Direct effects of vasoactive substances on superficial human veins in vivo can be investigated by measuring changes in the diameter of a superficial hand vein at a standardized congestion pressure before and after local infusion of the drugs. Changes in diameter at a given occlusion pressure reflect changes in venous tone. Experiments have been performed in healthy male volunteers; the diameter of a superficial hand vein was measured by means of a linear variable differential transformer. A series of ergot alkaloids (dihydroergotamine, ergotamine, methysergide and bromocriptine) were found to elicit a direct constrictor action when infused locally. Dihydroergotamine also produced marked and long-lasting venoconstriction after systemic i.v. and after oral administration. Studies on the mode of action of the venoconstrictor effect of ergot alkaloids suggest that alpha- and 5-TH-receptors are involved. Pizotifen and methysergide, both characterized as 5-HT-antagonists, were found to produce a marked, dose-dependent reduction of venous compliance when locally infused into superficial hand veins, suggesting partial agonist activity on 5-HT-receptors. The centrally-acting antihypertensive drug guanfacine was found to produce venoconstriction after local administration, probably due to its alpha-adrenoceptor stimulant effect. The venodilator effect of isoprenaline can be shown in veins preconstricted by noradrenaline. With nitroglycerin, venodilatation was observed by local infusions in veins not preconstricted.(ABSTRACT TRUNCATED AT 250 WORDS)