The luminal diameter of the radial artery was followed by high frequency ultrasound during 50 degrees head-up tilt-induced central volume depletion in ten healthy subjects of whom six were tilted twice and pretreated with the serotonin receptor antagonist methysergide or placebo following a double-blind randomized design. Eight subjects without active treatment experienced presyncopal symptoms after 16-45 (mean 32 min). Central volume depletion was indicated by an increase in mean thoracic electrical impedance [from 31.5 (SEM 1.6) to 33.4 (SEM 1.7) omega; P < 0.05]. Cardiac output decreased [from 4.1 (SEM 0.3) to 2.2 (SEM 0.3) 1.min-1] and heart rate [HR, from 64 (SEM 3) to 100 (SEM 7) beats.min-1], mean arterial pressure (MAP, from 77 (SEM 4) to 89 (SEM 2) mmHg [10.3 (SEM 0.53 to 11.9 (SEM 0.27) kPa]) and total peripheral resistance (TPR, from 19 (SEM 2) to 34 (SEM 4) mmHg.min.1-1 [2.5 (SEM 0.27) to 4.5 (SEM 0.53) kPa.min.1-1]) increased; but with the appearance of presyncopal symptoms, HR, MAP and TPR were reduced to 65 (SEM 8) beats.min-1, 46 (SEM 4) mmHg [6.1 (SEM 0.53) kPa] and 18 (SEM 3) mmHg.min.1-1 [2.4 (SEM 0.4) kPa.min-1.1-1], respectively (P < 0.05). Vascular resistance was reflected in the arterial diameter which decreased from 2.42 (SEM 0.17) to 2.27 (SEM 0.14) mm during head-up tilt and increased to 2.71 (SEM 0.14) mm with the appearance of presyncopal symptoms (P < 0.05). Methysergide reduced the resting radial (15 +/- 2%) and temporal artery diameters (10 +/- 3%) (P < 0.05); however, it affected neither tilt-tolerance nor the central cardiovascular response to tilt. The results suggested a serotonergic influence on arterial tone at rest, and demonstrated that vessels as large as the radial artery participated in vascular control during central volume depletion independent of such a serotonergic influence.