Endothelial function is known to predict cardiovascular disease. The aim of the present study was to examine whether endothelial function in smokers with normal cholesterol levels could be normalized by treatment with 80 mg of atorvastatin in comparison with a control group. Healthy smokers (n=20) and non-smokers (n=20) were randomized to receive 80 mg of atorvastatin or placebo in an open randomized cross-over study, followed by measurement of endothelial functional [FMD (flow-mediated dilation)]. At baseline, smokers had a lower FMD compared with the non-smoking group (2.2+/-0.5 and 4.5+/-0.8% respectively; P<0.05). In the smoking group, FMD increased significantly (P<0.05) to 4.0+/-0.8% during treatment with atorvastatin and returned to basal levels during placebo (2.3+/-0.6%). In the non-smoking group, FMD was unaffected by both atorvastatin and placebo. The net change of total cholesterol or LDL (low-density lipoprotein)-cholesterol was not associated with the net change in FMD when the study group was considered as a whole or the smoking group was considered separately. In conclusion, improved endothelial function was observed in a group of smokers when they were received 80 mg of atorvastatin, whereas atorvastatin had no effect on endothelial function in the non-smoking group. The improved FMD among smokers was independent of the decrease in LDL-cholesterol during atorvastatin treatment. The results show that poor endothelial function in smokers with normal lipid levels can be improved by a statin treatment.