The distribution of adrenergic nerves in guinea pig and rat liver was studied by the immunolocalization of fibers containing tyrosine hydroxylase and dopamine β-hydroxylase, enzymes involved in the synthesis of catecholamines. In both species, adrenergic fibers were identified within portal tracts, often in close proximity hepatic artery branches. In guinea pig liver, but not liver, abundant intraacinar fibers were identified; fibers were also seen within the walls of terminal hepatic vein radicles and larger hepatic veins. The presence of peptidergic nerves containing the regulatory peptide neuropeptide tyrosine and the C-flanking peptide CPON was investigated by indirect immunofluorescence. The distribution of these nerves was similar to that of tyrosine hydroxylase- and dopamine β-hydroxylase-positive nerves and showed the same species difference. The effector sympathetic nature of tyrosine hydroxylase- and neuropeptide tyrosine-positive fibers rat liver was confirmed by chemical denervation studies using 6-hydroxydopamine.