In brain, the monoamines, dopamine, norepinephrine, and serotonin, are confined to anatomically distinct neuronal systems, each of which furnishes widespread projections to neocortex. In primate, but not in rat, the terminal patterns of each of these systems have a high degree of regional and laminar specificity. These findings suggest that there are different sites of action and possibly different functional roles for each of the monoamines. This type of precise anatomic information is essential to our understanding of the possible involvement of monoamines in human disease states.