The present study investigated the circulating levels and cerebral fluxes of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) and their relation to cerebral blood flow (CBF) during normoventilation and hyperventilation in patients with fulminant hepatic failure (FHF). Sixteen patients with FHF were studied and compared to six patients with cirrhosis of the liver. CBF was measured by the (133)Xe wash-out technique. Blood samples were obtained simultaneously from the artery and internal jugular bulb. Concentrations of CGRP and VIP were higher in FHF than in cirrhosis, 87 (55-218) vs. 29 (21-42) pmol/L, and 11 (6-29) vs. 5 (3-9)pmol/L, respectively. NPY was normal, none of the measures were related to CBF, and there was no detectable net brain fluxes. Hyperventilation did not alter any of the measures. CGRP and VIP in FHF seem to reflect hemodynamic changes in the systemic rather than in the cerebral circulation.