Calcitonin gene-related peptide (CGRP), an endogenous vasoactive peptide encoded by the calcitonin gene in nerve cells, is distributed throughout the cardiovascular system and is a potent vasodilator. Plasma levels of CGRP have been elevated in animal models with sepsis. This study was designed to determine whether plasma CGRP levels are elevated in patients with sepsis and perhaps contribute to the hyperdynamic cardiovascular state in sepsis. Plasma CGRP levels were obtained from normal healthy volunteers and from patients with sepsis. Volunteers were afebrile and had normal pulse and blood pressure. Patients with sepsis were selected according to the following criteria: (1) temperature higher than 38.5 degrees C, (2) white blood count greater than 14,000/ml, (3) positive blood culture of bacterial organisms, (4) hemodynamic parameters consistent with hyperdynamic sepsis, and (5) negative history of thyroid or other endocrine abnormalities. CGRP was extracted and assayed by radioimmunoassay for iodine 125-labeled human CGRP. In patients with sepsis, the cardiac index was 5.4 +/- 0.5 L/min/m2 (normal, 3.0); systemic vascular resistance was 7.1 +/- 0.5 mm Hg/L/min (normal, 16); oxygen delivery was 1496 +/- 137 ml/min (normal, 1000). Plasma CGRP levels were significantly elevated in the patients with sepsis, 14.9 +/- 3.2 pg/ml, compared to plasma CGRP levels in control volunteers, 2.0 +/- 0.3 pg/ml (p less than 0.0005). These elevated levels of CGRP may contribute to the decreased vascular resistance and increased cardiac output in the hyperdynamic septic state.