The radial artery (RA) is increasingly used as coronary artery bypass graft. In rare cases, however, it is macroscopically atherosclerotic at time of harvest. We examined how the regulation of vascular tone is altered under such circumstances. Macroscopically evident atherosclerotic lesions were observed in 3 of 429 RA (0.7%) isolated within 2 years. Histology revealed severe plaque formation; however, von Willebrand Factor staining showed a morphologically intact endothelium (n = 3). Endothelium-dependent relaxations to acetylcholine (10(-5) M) were reduced in atherosclerotic RA (32 +/- 6%; n = 3) as compared with control (78 +/- 4%; n = 10; P = 0.0001). Receptor-independent contractions to KCl (100 mM) were reduced in atherosclerotic RA (33.19 +/- 5.06 mN; n = 3) as compared with control (108.02 +/- 15.76 mN; n = 9; P < 0.05). Similarly, contractions to thrombin (1 U/ml) were reduced in atherosclerotic RA (3.02 +/- 1.58 mN; n = 3) as compared with control (10.97 +/- 5.12 mN; n = 8). Likewise, receptor-mediated contractions to norepinephrine were reduced in atherosclerotic RA (27.64 +/- 12.48 mN; n = 3) as compared with control (82.74 +/- 11.36 mN; n = 9; P < 0.05). Atherosclerosis is rare in RA of patients with coronary artery disease, but it does occur. Atherosclerotic RA exhibits a dysfunction of both endothelium and vascular smooth muscle. This dysfunction may favor thrombus formation and accelerated atherogenesis. Therefore, atherosclerotic RA should not be used for coronary artery bypass grafting.