OBJECTIVE The mammalian liver receives both sympathetic and parasympathetic nerves that contain aminergic, cholinergic and peptidergic components. The intrahepatic distribution of nerve fibers are highly species-dependent; and also, even within one species, there are notable variations. To reveal the pattern and type of hepatic innervation in different species, we examined the distribution and density of these nerve fibers. METHODS The livers of rats, golden hamsters, guinea pigs, dogs and humans were used. Aminergic and peptidergic nerve fibers were identified by immunohistochemistry for tyrosine hydroxylase (TH), neuropeptide Y (NPY), substance P (SP), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), and galanin (GAL), and cholinergic fibers were identified by the acetylcholinesterase (AChE) neurohistochemistry method. RESULTS AChE-, TH-, NPY-, CGRP-, VIP-, and SP-positive nerves were observed in the connective tissue of the portal region, and they were in close contact with hepatic arteries, portal veins and bile ducts in all five species. Within the parenchyma of guinea pig, dog and human livers, TH-, NPY- and SP-positive fibers were observed, but no AChE- and CGRP-positive fibers were observed. In rat and hamster livers, no parenchymal nerve fibers could be demonstrated, but CGRP-, NPY- and SP-positive fibers were observed in the border of periportal areas. The density of CGRP-positive nerve fibers were slightly higher around bile ducts than around hepatic arteries and portal veins. GAL-positive fibers were not detected in any animal. CONCLUSIONS These data indicate that there were differences in the patterns of hepatic innervation among rats, golden hamsters, guinea pigs, dogs and humans. The data also show that: 1) in rat and hamster livers, hepatic functions may be regulated by both sympathetic and parasympathetic nerves in the portal region; 2) in guinea pig, dog and human livers they may be regulated by these fibers both in the interlobular region (parasympathetic and sympathetic systems) and in the intraparenchymal region (sympathetic system); and thus, 3) in the latter three species, hepatocytes and sinusoidal cells may be innervated by sympathetic nerves.