Patients with the metabolic syndrome have three or more of five cardiovascular risk factors and increased oxidative stress, arterial stiffness and pressor responses to exercise, which may contribute to their threefold greater risk for coronary heart disease. In addition to lowering basal blood pressure (BP), angiotensin receptor blockers (ARBs) may benefit metabolic syndrome patients by reducing oxidative stress, arterial stiffness, and pressor responses to exercise. Twelve patients, 7 women and 5 men, with the metabolic syndrome (aged 45 +/- 2 years, BP 145 +/- 5/85 +/- 2 mm Hg, waist girth 110 +/- 3 cm, triglycerides 186 +/- 23 mg/dL, HDL cholesterol 44 +/- 2 mg/dL, glucose 99 +/- 3 mg/dL) were studied off medications, while on modest sodium restriction ( approximately 100 mmol/d). Patients were randomized to the ARB losartan or placebo for 3 weeks then crossed over to the complement for 3 weeks. Studies were performed at the end of each phase following an overnight fast. Serum lipids and biomarkers of oxidative stress (F2-isoprostanes, thiobarbituric acid reacting substances) were unchanged by losartan, whereas large artery elasticity at rest, measured with the HDI PulseWave, increased from 13.6 +/- 0.7 on placebo to 16.2 +/- 1.1 mL/mm Hg on losartan, P <.05. Losartan lowered systolic BP pre-exercise from 142 +/- 3 to 131 +/- 3 mm Hg (P <.001) and systolic BP after 6 min of treadmill exercise from 192 +/- 6 to 169 +/- 5 mm Hg (P <.001). Losartan lowered systolic BP (-23 +/- 3 v -11 +/- 2 mm Hg, P <.05) and pulse pressure (-4 +/- 1 v -15 +/- 2 mm Hg, P <.05) more during exercise than rest. Losartan reduces the pressor response to exercise, perhaps by enhancing arterial compliance. In addition to lowering basal BP, angiotensin receptor blockade in patients with metabolic syndrome improves arterial compliance and reduces pressor reactivity to exercise.