The results of studies in animals indicate that in left ventricular. (LV) dysfunction and early heart failure, vasodilative-natriuretic mechanisms effectively antagonize vasoconstrictive-anti-natriuretic systems; this balancing effect contributes to preservation of circulatory and renal function. Progression to overt heart failure is characterized by a shift of this balance, with dysfunction of vasodilator systems and activation of vasoconstrictor systems. In patients, neurohumoral activation is observed early in asymptomatic LV dysfunction and is related to the severity, of LV dysfunction in the progression of the syndrome. Neurohumoral activation precedes overt heart failure, and it has independent prognostic value for the development of heart failure. Activation of the renin-angiotensin system and of the sympathetic nervous system, as well as the possible stimulation of vasopressin secretion, may contribute to the transition from LV dysfunction to heart failure and may, therefore, provide targets for early pharmacological intervention.