The effects of non-insulin-dependent diabetes mellitus (NIDDM) were investigated on the reactivity of human internal mammary artery (IMA) and saphenous vein (SV) rings obtained from coronary artery patients (CAP) undergoing coronary artery bypass surgery. In the presence of endothelium, the maximal contractile response and sensitivity (pD2) of IMA or SV to NA and ET-1 significantly increased in CAP with NIDDM relative to CAP only (controls). Removal of the endothelium markedly and significantly enhanced the maximal contractile response and sensitivity of IMA or SV to NA in CAP only, but did not induce a significant alteration in CAP with NIDDM compared to that in the presence of endothelium. The maximal contractile response and sensitivity of diabetic vessels with or without endothelium to NA were similar to values of corresponding vessels without endothelium obtained from nondiabetic CAP. The maximum contractions developed by NA or ET-1 were much greater in SV than that determinated in the IMA. Acetylcholine (ACh) and histamine produced endothelium-dependent relaxations in precontracted IMA and these effects of ACh and histamine significantly decreased in CAP with NIDDM. Endothelium-dependent relaxations stimulated by ACh were more pronounced in IMA than that determinated in the SV. In precontracted SV, histamine induced marked contractions that were significantly greater in CAP with NIDDM relative to CAP only. Endothelium-independent relaxations of vessels to sodium nitroprusside (SNP) were not influenced by NIDDM. Data indicate that NIDDM causes a deficit in the vasorelaxant activity of endothelium, leading to an increase in contractility of human IMA and SV. Data also suggest that IMA can be a better choice of graft for coronary occlusive disease than SV, specially in patients with NIDDM.