This study aimed at evaluating a possible relationship between cholesterol levels and ventricular electrical instability in human beings. Forty subjects (26 males and 14 females, mean age+/-SD 50.3+/-3.7 yr) with isolated hypercholesterolemia (> or =240 mg/dl) were selected from a population of 250 patients who attended the outpatient department of our institution for symptomatic extrasystolic activity (ventricular premature complexes >3,000/24 h). Subjects were randomly assigned to receive either simvastatin 40 mg/d or placebo for 3 consecutive months. After treatment, subjects in the simvastatin group presented a significant decrease of total cholesterol and LDL-cholesterol (p<0.001) and an increase of HDL-cholesterol levels (p<0.01), associated with a reduction of both QTc dispersion (p<0.001) and ventricular premature complexes (p<0.001). None of these changes were observed in the placebo group. At baseline, there was a relationship between cholesterol levels, ventricular premature complexes (VPC) (r=0.33, p<0.05) and QTc dispersion (r=0.41, p<0.01). After treatment, reductions in serum cholesterol levels correlated with decreases of both VPCs (r=0.37, p<0.01) and QTc dispersion (r=0.49, p<0.01). In subjects with isolated hypercholesterolemia simvastatin may reduce the cardiovascular risk associated with ventricular electrical instability.