The mesencephalon of the young domestic pig was studied by tyrosine hydroxylase (TH) immunocytochemistry and acetylcholinesterase (AChE) histochemistry with focus on the substantia nigra (SN), the ventral tegmental area (VTA), and related areas. The purpose was to obtain information on the organization of the mesencephalic, TH immunoreactive (TH-i), and dopaminergic areas of the pig, in order to provide the necessary background for the possible use of the pig as an alternative large animal experimental model for research on Parkinson's disease, including the use of encapsulated pig dopaminergic neurons for intracerebral xenotransplantation. Significant findings in the pig, compared to observations in other species, included the presence of prominent bundles of TH-i dendrites passing in a dorsoventral direction from pars compacta into pars reticulata at middle and caudal levels of the SN, and the presence of a distinct TH-i substantia nigra pars lateralis (SNL). Caudally in the pig mesencephalon, the retrorubral field (RRF) was found to be very extensive. The view of the RRF, SN, and VTA as parts of the same integrated system was indicated by the crisscrossing of TH-i dendrites at the transitions between these areas. Estimation of the number of TH-i neurons in the SN and the VTA showed that these nuclei were of equal size in the pig. Further, it was found that TH-i nerve cells were present in the midline between the VTA in the interfascicular and rostral linear groups. TH-i nerve cells were also present in the otherwise serotoninergic dorsal raphe nuclei, just as other TH-i cells formed a perirubral cell group. AChE-positive neurons were present in both SN and VTA, and appeared to have the same size and morphology as the TH-i neurons in these areas. Within both nuclei, there were local differences in the AChE staining density, but perhaps more significantly were some marked differences in the structure of the AChE-positive neuropil of the two areas. We anticipate that the present description of the cellular organization of the TH-i dopaminergic areas in the domestic pig ventral mesencephalon will be useful for the development of a nonprimate, large animal, experimental model of Parkinson's disease.