A brief survey of our knowledge of the morphological organization of central 5-HT neuronal systems across phylogeny has revealed the following facts: 1. The 5-HT neurons seem to have occurred early in phylogeny. These neurons are already well-developed in the brain of cyclostomes (lampreys) and other primitive living vertebrates. 2. A similar pattern of topographical distribution of 5-HT cell bodies has been found in most vertebrates. These neurons are particularly abundant within the raphe region of the brain stem, whereas the catecholamine cells are more laterally located. In birds and mammals, where the 5-HT systems are strikingly well-developed, a certain degree of lateralization of the 5-HT systems has been noticed. This lead to a close intermingling of 5-HT and CA elements in these vertebrates. 3. The 5-HT neurons may act as an important informative link between the CSF and the neural tissue. In all nonmammalian vertebrates, a multitude of 5-HT cells was seen to be in direct contact with the CSF through short, club-like processes. The dense supraependymal plexus of 5-HT fibers disclosed in the rat brain could be the mammalian counterpart of these typical CSF-contacting cells. 4. The central 5-HT systems appear to be widespread and highly collateralized in all vertebrates. A single 5-HT raphe neuron may send divergent axon collaterals to various remote forebrain areas and, thus, could exert a rather diffuse influence over vast neuronal populations in all species. 5. The terminal arborizations of the 5-HT systems display patterns which are strikingly constant from one vertebrate class to another. Such a constancy in the structural organization of the 5-HT neurons strongly suggests that these neuronal systems are indeed phylogenetically ancient and subserve similar fundamental brain functions in all vertebrates.