Accelerated atherosclerosis is a major risk for uremic patients undergoing long-term hemodialysis. Because hyperhomocysteinemia may influence this condition, 168 such patients were examined for a possible association between plasma total homocysteine concentration (tHcy) and conventional cardiovascular risk factors. Generalized atherosclerosis was indicated by excessive intimal-medial wall thickness (IMT) of the extracranial carotid artery as measured by B-mode ultrasonography. The results documented tHcy in these patients of 33.0+/-16.9 mu mol/L, a significantly higher amount than that of healthy subjects (11.0+/-3.1 mu mol/L, p<0.0001). The patients' carotid maximum IMT was 1.79+/-1.16 mm. In multiple regression analyses with forward elimination procedure, carotid maximum IMT was clearly related to age (r=0.417, p<0.0001), systolic blood pressure (r=0.262, p=0.0043), smoking (r=0.177, p=0.0076), duration of hemodialysis (r=0.083, p=0.0045), and tHcy (r=0.195, p=0.0021). These 5 factors accounted for 36.0% of the variation in carotid maximum IMT. Factors determined as unrelated were male gender, diastolic blood pressure, body mass index, total and HDL cholesterol, triglyceride, lipoprotein(a), uric acid, calcium, inorganic phosphate, and parathyroid hormone. Therefore hyperhomocysteinemia, along with advanced age, systolic hypertension and smoking aggravates atherosclerosis in chronic uremic patients.