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Background and Aims. Intracellular calcium regulation in endothelial cells depends on transient receptor potential channels (TRPs). Canonical TRPs (TRPCs) are now recognized as the most important Ca2+-permeable cation channels in vascular endothelium and TRPC3 channel is reported to play a role in vasodilation in animal vessels. However, little is known about the role of TRPCs in human arteries. We therefore tested the hypothesis that TRPCs play a role in human arteries. Methods. Cumulative concentration-relaxation curves to acetylcholine (-11 to -4.5 log M) were established in the human internal mammary artery (IMA) rings (n = 42) taken from 28 patients undergoing coronary artery bypass grafting in precontraction induced by U46619 (-8 log M) in the absence or presence of SKF96365 (10 mu mol/L) or Pyr3 (3 mu mol/L). Protein expressions of TRPC3 were determined by Western blot and immunohistochemistry staining. Results. The maximal relaxation induced by acetylcholine was significantly attenuated by the nonspecific cation channels inhibitor, SKF96365 (48.2 +/- 3.7 vs. 66.0 +/- 0.9% in control, p lt 0.01) or the selective TRPC3 blocker, Pyr3 (58.4 +/- 2.3% vs. 67.7 +/- 1.1% in control, p lt 0.01). Protein expression of TRPC3 was detected in human 1MA. Conclusions. TRPC3 exists and plays a role in the acetylcholine-induced endothelium-dependent relaxation in the human IMA. This study suggests that TRPC3 may be a potential new target in endothelial protection in patients with endothelial dysfunction such as in patients with coronary artery disease in order to improve the long-term patency of the grafting vessels.