The mammalian striatum is divided into compartments that are anatomically and neurochemically distinct. The dorsal striatum has been described as containing two compartments, striosomes and matrix, while the ventral striatum is thought to have a more complex, multi-compartmental organization. In this study, we sought to characterize the compartmentalization of the dorsal and ventral portions of the human striatum using choline acetyltransferase as a marker. Image analysis was used to assess relative densities of immunostaining, and three distinct, choline acetyltransferase-immunostained compartments were demonstrated: intensely immunostained, moderately immunostained and weakly immunostained areas. The dorsomedial portion of the striatum was made up of moderately immunostained regions embedded within a densely immunostained background, thus manifesting the characteristic striosome/ matrix organization of the dorsal striatum. However, the ventral and lateral two-thirds of the striatum were made up of a mixture of densely immunostained, moderately immunostained and weakly immunostained areas, with the moderately immunostained region forming the bulk of the background tissue, and smaller, densely immunostained and weakly immunostained regions embedded within it. These compartments were compared to regions defined by distinct levels of acetylcholinesterase immunostaining in adjacent sections; the staining patterns produced by the two cholinergic markers were found to be identical except in some portions of the nucleus accumbens, where acetylcholinesterase immunostaining was found to be more intense than choline acetyltransferase immunostaining. The immunoreactive somata were mapped within sections stained for choline acetyltransferase taken from different rostrocaudal levels of the striatum, and the distributions and densities of immunoreactive somata within these three cholinergic compartments were determined. In general, the densities of cholinergic somata roughly correlated with immunostaining intensity of regions, e.g. the most intensely immunostained compartment also had the highest densities of cholinergic somata. However, in the rostroventral striatum, the densities of cholinergic somata in the weakly immunostained compartment roughly equalled the densities of cholinergic somata in the moderately immunostained compartment, suggesting that local axonal arborizations of cholinergic cells may differ in density or orientation between the two compartments, or, alternatively, that some of the cholinergic cells in the weakly immunostained compartment may project outside of the striatum. The large proportion of striatum displaying ventral striatal characteristics (a complex, multi-compart-mental organization) in humans relative to that observed in other mammals suggests that the role of the ventral striatum may be expanded and more highly differentiated in the human brain.