We have previously demonstrated that short-term infusion of calcitonin gene-related peptide (CGRP) has beneficial effects in congestive heart failure. The effects of prolonged infusion of CGRP on hemodynamic functions, plasma hormones and renal blood flow were studied in 9 patients with congestive heart failure (New York Heart Association class III or IV, ejection fraction <35%). Hemodynamic variables were measured at 30-minute intervals for 8 hours during CGRP infusion (8 ng/kg/ min) and for 2 hours after discontinuation. CGRP caused a decrease in right atrial (28%, p < 0.05), pulmonary artery (22%, p < 0.02), pulmonary artery wedge (37%, p < 0.001) and systemic arterial (18%, p < 0.05) pressures. Systemic vascular resistance decreased more than pulmonary vascular resistance. Cardiac output (72%, p < 0.001) and stroke volume (60%, p < 0.02) increased. Heart rate did not change. There was no evidence of tolerance throughout the infusion. The hemodynamic effects were lost within 30 minutes of stopping CGRP. Renal blood flow (34%, p < 0.01) and glomerular filtration rate (43%, p < 0.01) increased. Atrial natriuretic peptide decreased (p < 0.05), while plasma cortisol (p < 0.02) increased. Plasma epinephrine, norepinephrine, renin activity, aldosterone and growth hormone were unchanged. It is concluded that in patients with severe congestive heart failure, CGRP has sustained beneficial effects on hemodynamic functions and has no adverse effects on hormones. Unlike many other vasodilators, CGRP also increases renal blood flow and glomerular filtration.