To evaluate the effects of short-term cholesterol-lowering treatment on myocardial effort ischemia, 22 patients with stable effort ischemia and mild to moderate hypercholesterolemia (low density lipoprotein [LDL] cholesterol 160 to 220 mg/dl) were randomly allocated at baseline (TO) in 2 groups. Group A included 12 patients treated with simvastatin 10 mg bid; group B included 10 patients treated with placebo. All patients underwent a treadmill electrocardiography (ECG) test; total cholesterol, HDL and LDL cholesterol, triglycerides, plasma, and blood viscosity were measured. All tests were repeated after 4 and 12 weeks. For 18 of the same patients (11 taking simvastatin, 7 receiving placebo), forearm strain-gouge plethysmography was performed at baseline and after 4 weeks, both at rest and during reactive hyperemia. At 4 and 12 weeks, group A showed a significant reduction in total cholesterol (p <0.05) and LDL (p <0.05), with unchanged HDL, triglycerides, blood, and plasma viscosity. Effort was unmodified, ST-segment depression at peak effort and ischemic threshold were significantly improved after 4 and 12 weeks (all p <0.05) with unchanged heart rate x systolic blood pressure product. A significant increase in the excess flow response to reactive hyperemia was detected in group A (p <0.03); group B showed no changes in hematochemical and ergometric parameters. These data suggest that cholesterol-lowering treatment is associated with an improvement in myocardial effort ischemia; this might be explained by a more pronounced increase of coronary blood flow and capacity of vasodilation in response to effort.