Although epidemiological studies suggest that people with minor impairment of renal function are at higher risk of stroke and coronary heart disease, the mechanisms underlying this relation are unclear. One explanation may lie with observations that deterioration in renal function is accompanied by elevations in plasma homocysteine concentrations. There is evidence that moderate hyperhomocysteinemia may play a causal role in atherosclerotic disease. We investigated the relations between renal function, plasma homocysteine and atherosclerosis of the carotid arteries in 128 men and women aged 69-74 years. Renal function was assessed by creatinine clearance and serum creatinine. Duplex ultrasonography was used to quantify the degree of stenosis in the extracranial carotid arteries. Severity of carotid atherosclerosis was greatest in men and women with the poorest renal function, whether measured by creatinine clearance or serum creatinine. After adjustment for plasma homocysteine, pulse pressure and other cardiovascular risk factors, the odds ratio for having carotid stenosis >30% was 4.3 (95% CI 1.4-12.9) in those whose creatinine clearance rate was 55 ml/min or less compared with those whose creatinine clearance rate was >73 ml/min. Even small decrements in renal function were associated with increased risk; people whose creatinine clearance rate was between 56 and 73 ml/min had an odds ratio of 3.8 (95% CI 1.2-11.9). Plasma homocysteine concentrations were significantly higher in people with poorer renal function, but they did not explain the associations we found between carotid atherosclerosis and creatinine clearance or serum creatinine.