Hyperhomocysteinaemia is an established risk factor for vascular disease. The only source of homocysteine in humans is the amino acid methionine found in dietary protein. In an 8-week study, fasting plasma homocysteine concentrations were examined in a group of healthy male subjects (n = 6) under usual dietary conditions (weeks 1-4) and in response to weekly graded (25, 50 and 75 mg/kg/d) supplementary methionine (weeks 5, 6, 7). Nutrient intakes, including methionine, were calculated from 4 x 3 day food records. Under usual dietary conditions (mean methionine intake; 0.95 +/- 0.51 mg/d) weekly mean plasma homocysteine concentrations for the group were not significantly different (ANOVA) from each other ranging from 6.82 +/- 1.77 to 9.42 +/- 2.73 mumol/l. Doubling (supplementing with 25 mg/kg/d; + 2.04 g/d) or quadrupling (50 mg/kg/d; + 4.08 g/d) methionine intakes did not result in a significant increase in plasma homocysteine (8.56 +/- 3.68 mumol/l and 13.37 +/- 5.09 mumol/l respectively). A significant increase, however, was achieved when diets were supplemented with methionine at the highest level of 75 mg/kg/d (+6.14 g/d) resulting in a mean plasma homocysteine concentration of 18.05 +/- 11.8 mumol/l. Mean plasma homocysteine concentration returned to baseline (8.76 +/- 3.42 mumol/l), 10 days post-supplementation. The results of this study indicate that an increased dietary methionine will only cause elevated fasting homocysteine concentrations if ingested at intakes equivalent to five times usual intake. Because it is very unlikely that such levels could be achieved through dietary means alone we conclude that plasma homocysteine is unlikely to be affected by longer-term changes in food methionine intake.