Blood pressure control in mild and moderate hypertension may reduce morbidity and mortality. On the other hand, antihypertensive drugs may cause adverse metabolic, electrolyte, neural and hemodynamic alterations that detract from their effectiveness. The effect of hydrochlorothiazide (HCTZ) on some of these factors was compared with that of HCTZ and a sympatholytic drug in 20 hypertensive patients with left ventricular hypertrophy and retinopathy. HCTZ controlled blood pressure at rest and during maximum treadmill exercise (-12 mm Hg systolic and diastolic pressure (p less than 0.05), reduced left ventricular mass by 7% (p less than 0.05) and lessened aerobic impairment at maximum treadmill exercise by 45% (p less than 0.05). These effects were further improved after "neural blockade." A potential adverse effect of HCTZ--hypokalemia (-0.6 mEq/liter, p less than 0.01)--and the associated incidence of ectopy during effort (50%) were lessened after neutralizing neural tone. Combination therapy with low-dose diuretic and sympatholytic drugs was effective and well tolerated in patients with cardiac and vascular sequelae of moderately severe hypertension.