The alpha-adrenergic component of the sympathetic nervous system plays a major role in the pathophysiology, clinical manifestations, and natural history of human congestive heart failure. While the augmentation of alpha-adrenergic tone (through the neuronal release of norepinephrine) is a valuable mechanism to maintain adequate systemic blood pressure and perfusion of vital organs in states of circulatory collapse, stimulation of alpha-adrenergic receptors produces detrimental hemodynamic effects in congestive heart failure. These undesirable effects result from alpha-mediated vasoconstriction and consist of excessive elevation of right and left ventricular filling pressures and pulmonary and systemic vascular resistances. The enhancement of alpha-adrenergic tone preferentially reduces blood flow to the hepatosplanchnic circulation. Many of the hemodynamic responses that are seen after activation of the renin-angiotensin system are related to the ability of angiotensin II to amplify the actions of the alpha-adrenergic system. Stimulation of myocardial alpha-adrenergic receptors in most species elicits a modest positive inotropic effect, but the presence and importance of this property in the human heart remains controversial. Chronic stimulation of myocardial alpha-adrenergic receptors may result in the hypertrophy of cardiomyocytes and may also contribute to the development of catecholamine-induced cardiomyopathy. Acute blockade of the heightened alpha-adrenergic tone in congestive heart failure (e.g., with first doses of prazosin) results in favorable hemodynamic effects, but repeated dosing leads to pharmacological tolerance. Consequently, the long-term administration of alpha-adrenergic blocking agents in human heart failure has not been accompanied by an improvement in clinical status, exercise capacity, or survival.(ABSTRACT TRUNCATED AT 250 WORDS)