The long-term efficacy of coronary artery bypass graft (CABG) surgery is limited by saphenous vein graft (SVG) disease. Elevated levels of plasma homocysteine are a known independent risk factor for cardiovascular disease. However, its influence on the patency of SVG is unknown. To determine whether plasma homocysteine levels are related to SVG disease after CABG we measured homocysteine levels in 80 patients who underwent CABG (age: 64+/-8, interval after bypass surgery: 6.4+/-3.1, range: 1-13 years). The patients were divided into a vein graft disease group (more than 50% angiographical stenosis in any vein graft, n=40) and a no-vein graft disease group (<50% stenosis in any vein graft, n=40). The presence of a mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene was also determined by polymerase chain reaction. Homocysteine levels in the vein graft disease group were significantly higher than in the no-vein graft disease group (11.2 vs. 9.1 micromol/l, p=0.01). Multiple regression analysis showed that the interval after CABG was an independent factor for SVG disease (odds ratio: 1.014, 95% confidence intervals: 1.003-1.025, p=0.013) and elevated levels of homocysteine tended to be an independent factor for SVG disease (odds ratio: 1.098, 95% confidence intervals: 0.994-1.213, p=0.067). There was no significant difference in MTHFR genotypes between the two groups. These findings indicate that elevated levels of plasma homocysteine are related to SVG disease after CABG.