BACKGROUND: Generalized atherosclerosis is increasingly recognized as an important cause of end-stage renal disease (ESRD). We questioned to what extent atherosclerotic risk factors determine renal function in the general population. METHODS: We used baseline data of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) Study. A total of 8592 subjects, aged 28 to 75 years old, visited the outpatient clinic for blood pressure and anthropometric measurements, fasting blood sampling, and delivery of two 24-hour urine collections for creatinine clearance and albuminuria calculations. Design-based multivariate linear regression was used to estimate renal function. RESULTS: In a multivariate model, male gender and body mass index (BMI) were associated with a higher renal function, while increasing diastolic blood pressure, serum triglycerides, use of antihypertensive or lipid-lowering medication were associated with a lower renal function. Age, systolic blood pressure, and plasma glucose showed an inverse U-shaped relationship with renal function. Cholesterol/high-density lipoprotein (HDL) ratio, smoking, and antidiabetic medication did not contribute to explain renal function. The atherosclerotic risk factors were related to renal function independently of albuminuria or C-reactive protein (CRP). Albuminuria and CRP itself were also related to renal function. Following gender and age, BMI, urinary albumin excretion (UAE), and plasma glucose had the strongest relation with renal function. CONCLUSION: We conclude that differences in renal function in the general population are (partly) explained by various atherosclerotic risk factors. Some risk factors are associated with elevated filtration, some with an impaired filtration, and others with both a higher and a lower renal function.