In advanced cirrhosis and hepatorenal syndrome, peripheral vasodilation is a prominent feature and may be pathophysiologically relevant. To determine whether the potent vasodilator, calcitonin gene-related peptide (CGRP), circulates at abnormal levels in patients with these disorders, we observed eight patients with alcoholic cirrhosis and hepatorenal syndrome, seven with alcoholic cirrhosis and ascites without hepatorenal syndrome, and 10 healthy controls. Plasma CGRP levels were higher in patients with alcoholic cirrhosis and hepatorenal syndrome (364 +/- 166 pg/ml) than in healthy controls (143 +/- 54 pg/ml, p less than 0.01). In patients with cirrhosis and ascites without hepatorenal syndrome, plasma CGRP levels were less elevated (291 +/- 257 pg/ml, NS). The identity of immunoreactive CGRP and synthetic hCGRP was confirmed by high performance liquid chromatography. These results suggest that CGRP may play a role in hepatorenal syndrome. However, to establish whether circulating CGRP contributes to the hemodynamic change in hepatorenal syndrome requires study of a larger number of patients and additional control groups.