This chapter has reviewed biochemical and morphological studies of the human and monkey serotonergic system. In addition, the serotonin-producing neurons of M fascicularis were analyzed, using immunocytochemistry, radioautography, and measurements of synaptosomal serotonin reuptake and supernatant tryptophan hydroxylase activity. The major sections of the chapter covered cell bodies, pathways, subcortical distribution, and cortical distribution, and a gross brain dissection guide of M fascicularis is included. An atlas of the 5-HT-IR cell bodies was presented in Figures 7 to 33. Rostral and caudal groups of nuclei were discussed. The rostral group consists principally of the nuclei raphe dorsalis (B7 and B6), centralis superior (B8, B5, and part of B7), and prosupralemniscus (B9). These groups ascend mainly in tracts lying outside the medial forebrain bundle (MFB). In M fascicularis, 25% of the fibers within the MFB are myelinated. The caudal 5-HT-IR nuclei consist principally of the nuclei in a dorsal cluster (raphe obscurus, B2) and in a ventral cluster (pallidus, B1, and magnus B3). The dorsal 5-HT-IR cells in raphe obscurus are associated with the MLF, and cells extend into cervical spinal cord (lamina IX and X) with the descending MLF and the TTS. Fibers from the raphe obscurus innervate the motoneurons in both the cranial nuclei (X, XII) and the ventral horn. The ventral 5-HT-IR cells lie mainly medial to the medial leminiscal fibers. A large number of these cells extend laterally into paragigantocellularis lateralis and here extend caudally lying below the lateral reticular nuclei. Cells from this group are seen dorsally joining the internal arcuate fibers. The raphe magnus of the ventral cluster projects to the dorsal horn and is believed to mediate the serotonin-induced analgesia. The descending fibers from both of these clusters are occasionally myelinated. Also, in our tryptophan- and pargyline-pretreated monkeys, small 5 HT-IR cells were visible in the area postrema. Human and monkey biochemical data (detailed summary in Tables 1-6) provide evidence for the presence of serotonin fibers in all cortical and subcortical regions. In subcortical regions, the midbrain, medulla, amygdala, and substantia nigra have the highest, whereas the cerebellum, spinal cord, and ventral pons have the lowest amount of serotonin and its metabolite, 5-HIAA. In the basal ganglion, the globus pallidus has the highest rate of 5-HT synthesis. The temporal lobe receives the most serotonin of the major cortical lobes.(ABSTRACT TRUNCATED AT 400 WORDS)