We previously demonstrated that normotensive patients with hypercholesterolemia showed excessive blood pressure (BP) responses to stress tests. In this study, we examined the effects of cholesterol-lowering therapy on BP in order to confirm that hypercholesterolemia plays a role in the regulation of BP. Fifteen patients with hypercholesterolemia and 24 normal cholesterolemic controls performed mental arithmetic stress (AS) and hand grip (HG) tests. BP was measured during the tests. Serum lipids and lipid peroxides were measured before the AS. Platelet intracellular free calcium concentration ([Ca2+])i with and without low density lipoprotein (LDL) stimulation, plasma cGMP and NOx were determined immediately before AS and at the end of each test. In hypercholesterolemic patients, the tests were repeated at the end of a 12-week treatment with 10 mg/day of pravastatin, a hepatic hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. In hypercholesterolemic patients, BP responses to both tests were greater than those of the controls. Basal and LDL-stimulated platelet [Ca2+]i were higher, and the ratio of plasma cGMP to NOx was lower. Serum total cholesterol, LDL cholesterol and lipid peroxides were significantly decreased in association with the pravastatin treatment. Systolic BP to AS and systolic BP/diastolic BP to HG were decreased (p < 0.01, p < 0.01/p < 0.02, respectively). Platelet [Ca2+]i with LDL stimulation was decreased (p < 0.01). Plasma cGMP was increased (p < 0.05), whereas NOx was decreased (p < 0.05); therefore, the ratio of cGMP to NOx was increased (p < 0.05). In conclusion, excessive blood pressure responses to stress tests were improved after cholesterol-lowering therapy. This finding suggests that hypercholesterolemia itself is involved in the regulation of BP.