Hyperhomocyst(e)inemia (plasma homocyst(e)ine concentration >16.0 micromol/l) is an independent risk factor for atherosclerosis, and is ubiquitous in patients with end-stage renal disease (ESRD). Oral folate supplementation in the non-ESRD population has been demonstrated to reduce plasma homocyst(e)ine (Hcy) concentration, and may reduce atherosclerotic morbidity. This study was undertaken to evaluate the efficacy of folate supplementation in reducing Hcy in patients with ESRD and cardiovascular disease. Twenty-eight chronic hemodialysis patients with demonstrated hyperhomocyst(e)inemia (mean Hcy 35.2+/-13.3 micromol/l) were enrolled in the study. The presence of atherosclerosis was documented by history, physical examination, or ultrasonographic criteria. Hcy was determined initially and following six weeks' supplementation with 5.0mg folate and multvitamins. Hcy fell a mean of 15.0+/-10.4 micromol/l (38.9+/-19.9%) following supplementation (p16.0 micromol/l (p=0.02). A significant positive correlation was observed between initial Hcy and both absolute and percent reduction after folate supplementation (r=0.87, p16.0 micromol/l in the majority of patients, however, despite large absolute reductions in Hcy. Doses of folate greater than 5mg, or additional therapy may be required to further reduce Hcy in the majority of ESRD patients.