Beyond their hypolipidemic effect, statins reduce cardiovascular risk in hypertensive subjects via various mechanisms; one suggested mechanism is that they reduce sympathetic activity. We investigated the hypothesis that simvastatin decreased muscle sympathetic nerve activity (MSNA) in 31 hypertensive subjects with hypercholesterolemia (aged 38.7 ± 10 years). In this randomized, placebo-controlled, double-blinded study, patients were treated with simvastatin (40 mg day(-1); n=15) or placebo (n=16) for 8 weeks. Before and after treatment, we measured MSNA, blood pressure and heart rate. Baroreceptor control of the heart rate, or baroreceptor sensitivity (BRS), was computed by the sequence method, a cross-analysis of systolic blood pressure and the electrocardiogram R-R interval. Blood samples were tested for plasma levels of catecholamines, neuropeptide Y, aldosterone, endothelin and renin activity. Simvastatin significantly reduced MSNA (from 36.5 ± 5 to 27.8 ± 6 bursts per min, P=0.001), heart rate (from 77 ± 6.7 to 71 ± 6.1 beats per min, P=0.01) and both total and low-density lipoprotein cholesterol (from 249 ± 30.6 to 184 ± 28.3 mg dl(-1), P=0.001 and from 169 ± 30.6 to 117 ± 31.2 mg dl(-1), P=0.01, respectively). Simvastatin also improved BRS (from 10.3 ± 4.1 to 17.1 ± 4.3 ms per mm Hg, P=0.04). No changes were observed in systolic or diastolic blood pressures, or in plasma levels of catecholamines, neuropeptide Y, endothelin, aldosterone and renin activity. After simvastatin therapy, MSNA and BRS were inversely related (r=-0.94, P<0.05). In conclusion, we found that, in patients with hypertension and hypercholesterolemia, simvastatin reduced MSNA, and this was related to increased baroreceptor sensitivity.