Six patients with chronic congestive cardiac failure, who had never received any drug treatment, were studied before and after one month of therapy with frusemide alone at a dose of 40 mg a day. Measurements were made at rest of plasma epinephrine, norepinephrine, renin activity, aldosterone, atrial natriuretic peptide, cortisol, growth hormone and prolactin, together with central hemodynamics, body fluid volumes and renal function. The initial measurements of hemodynamics, body fluid compartments and renal function confirmed the presence of the physiopathology typical of congestive cardiac failure. Plasma concentrations of norepinephrine, atrial natriuretic peptide, aldosterone and growth hormone were significantly increased. The mean value of plasma renin activity, although high, was not significantly different from normal. After one month of treatment, body weight, body fluid volumes and exchangeable sodium were reduced. Hemodynamics and renal plasma flow and glomerular filtration were not significantly affected. Plasma norepinephrine fell to within normal limits; atrial natriuretic peptide increased significantly; plasma renin activity and cortisol increased to levels which were abnormally high; growth hormone increased to levels similar to those associated with acromegaly. Increased circulating concentrations of atrial natriuretic peptide during treatment by frusemide may have an important influence on the kidney, blood vessels and neuro-endocrine response.