The objective of this study was to investigate the effects of lipid-lowering treatment on renal function in patients with peripheral arterial disease (PAD). This was a retrospective study of hyperlipidemic claudicants referred to a vascular surgery and risk modification clinic. Serum creatinine and urate concentrations and the fasting lipid profile were measured pretreatment and after 3-4 months of treatment with 20 mg/day simvastatin. In 103 consecutive patients with PAD (57 men; 46 women), median age 67 years (range: 51 to 83) there was a significant decrease in serum creatinine from a mean (SD) of 87 (12) micromol/L pretreatment to 84 (12) micromol/L post-treatment (p<0.0001). This difference was more marked in the tertile of patients with the highest baseline creatinine levels. There was also a significant reduction in serum urate from 0.37 (0.07) mmol/L to 0.35 (0.07) mmol/L (p<0.0001). Both these effects were independent of the degree of total cholesterol (TC) or low-density lipoprotein (LDL) cholesterol reduction. There was a significant reduction in TC from 6.6 (1.0) to 5.2 (0.8) mmol/L and LDL cholesterol from 4.3 (1.0) to 2.8 (0.7) mmol/L; both p<0.0001. Significant improvement also occurred in the high-density lipoprotein cholesterol and triglyceride levels. Cholesterol lowering with simvastatin 20 mg/day improved indices of renal function after 3-4 months of treatment in hyperlipidemic patients with PAD. Further studies are needed to establish and define the clinical relevance of these findings, especially in patients with different degrees of renal failure.