1. Most of the current knowledge concerning the fine structure of serotonin (5-HT) neurons in mammalian CNS is derived from radioautographic studies following uptake of tritiated 5-HT in vivo. 2. (3H)5-HT-labelled perikaria and proximal dendrites have thus far been visualized ultrastructurally in nuclei raphe dorsalis, paragigantocellularis lateralis and dorsomedialis hypothalami. In none of these regions were they found to possess cytological features which would constitute a hallmark of their serotoninergic nature. 3. Most central 5-HT neurons give rise to thin and unmyelinated, albeit long and ramified axons. These innervate the entire neuraxis, issuing billions of varicose terminals along their paths. Such varicosities usually consist of small axonal enlargements (0.5-1 micrometers in diameter) containing clustered vesicular organelles. These organelles include small (15-50 nm), pleomorphic agranular vesicles and larger (50-130 nm), round or flattened dense-cored vesicles. 4. A salient feature of central 5-HT varicosities is that they often lack the junctional complexes classically considered as the morphological substrate for chemical transmission in CNS. The occurrence of synaptic specializations varies from one brain region to another. When present, synaptic contacts are generally found on dendritic branches or spines of nonserotoninergic neurons, but axo-somatic or axo-axonic synapses, as well as contacts with 5-HT elements, have also been reported. The frequency with which 5-HT varicosities establish junctional relationships may be more dependent on the territory of innervation than characteristic of any subset of 5-HT fibers or nerve cell bodies. 5. It is currently assumed that both non-junctional and junctional 5-HT varicosities can release their endogenous amine upon axonal depolarization. This mode of action, which evokes that of a local neurohormone, might subtend the modulatory effects of 5-HT in the CNS.