The aim of this study was to determine whether tumor necrosis factor (TNF)-α would impair basal and stimulated endothelium-dependent vasomotion in human resistance vessel. Changes in baseline and acetylcholine (ACh)-induced forearm vascular resistance (FVR) were measured plethysmographically before and after a low-dose intraarterial forearm infusion of TNF-α according to the following three protocols in healthy volunteers. In the condition without pretreatment, basal FVR was significantly increased by TNF-α (from 30.5±4.8 to 39.9±5.9 units; p< 0.01), whereas ACh-induced minimal FVR did not differ between pre-and post-TNF-α states. In the condition after pretreatment with the cyclooxygenase inhibitor acetylsalicylic acid, although the vascular effects of TNF-α on basal FVR appeared to be blocked (37.1±5.3 vs. 37.6±5.2; NS), ACh-induced minimal FVR did not differ between pre-and post-TNF-α states. In the condition after pretreatment with the nitric oxide (NO) synthase inhibitor N G-monomethyl-L-arginine, the vascular effect of TNF-α on basal FVR was diminished, and the ACh-induced maximal dilatory response was significantly blunted after TNF-α compared with before TNF-α (minimal FVR: 30.4±12.0 vs. 12.3±4.2 units; p< 0.05). These findings suggest that brief exposure of the human forearm resistance artery to TNF-α may increase basal bioavailability of the vasoconstrictor prostaglandin and reduce basal bioavailability of NO. In the stimulated condition, TNF-α-induced vascular dysfunction may be overwhelmed by increased NO bioavailability in healthy humans.