BACKGROUND: Hyperhomocysteinemia and lipid abnormalities are commonly found in patients with chronic renal failure; both are recognized as risk factors for atherosclerosis. The homocysteine-lowering effect of pyridoxine is controversial. This study was performed to determine the effect of a high dose of pyridoxine (300 mg i.v. three times a week) on plasma and red blood cell lipid profile and plasma homocysteine concentration in twelve chronic renal failure patients on regular hemodialysis. Fasting blood samples were taken at the beginning of the study (basal 1), after 30 and 60 days of treatment and 4 months after withdrawal (basal 2). RESULTS: Pyridoxine supplementation induced a significant decrease in total plasma homocysteine level and also a lowering effect in plasma total cholesterol and triglycerides. These biochemical data increased when the samples were taken at basal 2, reaching the levels obtained at the beginning of the experiment. LDL cholesterol increased whereas HDL cholesterol was reduced during the treatment. In erythrocyte membranes vitamin B6 therapy enhanced the cholesterol/phospholipid ratio as well as the fluorescence anisotropy of diphenyl-hexatriene. CONCLUSIONS: We conclude that high doses of pyridoxine represent an effective strategy to ameliorate both plasma homocysteine levels and lipid profiles in chronic renal failure patients, protecting them from atherosclerosis. Further research using a long-term treatment would be necessary in an attempt to restore the fatty acid pattern and the fluidity of red cell membranes.