The primary hemodynamic hallmark of essential hypertension is elevated systemic vascular resistance that may be affected by increased sympathetic tone, activation of the renin-angiotensin system, or structural and cellular abnormalities (e.g., those involving calcium) of the blood vessel wall. The aim of therapy, therefore, is to reduce vascular tone through the use of a specific blocker of neurohormonal mechanisms or a nonspecific vasodilator. These agents are not equally effective in all patients. In comparing these drugs, the following issues are important: pathophysiology, patient demography, mechanism of drug action, long-term efficacy, and metabolic effects. Several studies have suggested that there is a response to angiotensin converting enzyme inhibitors in young and middle-aged patients, whereas in elderly patients there may be more of a response to calcium channel blockers. Alpha 1-adrenergic blockers, however, appear to be effective in all age groups. Calcium channel blockers and alpha 1-adrenergic blockers generally are more effective in black patients than are angiotensin converting enzyme inhibitors. Neither of these agents adversely affects serum potassium, glucose, or plasma lipid levels. In fact, data suggest that alpha 1-adrenergic blockers may reduce low-density lipoprotein cholesterol and triglyceride levels and increase high-density lipoprotein cholesterol levels. Unlike alpha-adrenergic blockers and angiotensin converting enzyme inhibitors, calcium channel blockers may produce a negative inotropic effect and improved cardiac diastolic relaxation. In addition to all of these factors, it is important that the agent selected as initial antihypertensive therapy be efficacious, have a favorable side-effects profile, and have no adverse influences on other risk factors.