We have employed immunohistochemical and morphometric procedures to study serotonin-synthesizing (PH8-immunoreactive) neurons in the pontine reticular formation of the adult human. PH8-immunoreactive neurons were found in three cytoarchitectural regions: the median rahpe nucleus (MnR), oral pontine reticular nucleus (PnO), and supralemniscal region (group B9). On the basis of cell size, morphology, and position, it was possible to distinguish distinct subgroups within the MnR (dorsal, midline, and paramedian cell clusters) and within the PnO (dorsal and central cell clusters), whereas within the B9 there were no distinct cell clusters. We have estimated that there are approximately 125,000 PH8-immunoreactive neurons in the human pontine tegmentum; 64,400 in the MnR, 30,700 in PnO and 29,000 in B9. The large numbers of serotonin-synthesizing neurons in the human pontine tegmentum contrasts with their relative paucity in nonprimate species such as rats and cats. Nonhuman primates also have large numbers of pontine serotonergic neurons but the morphology of these neurons and their spatial arrangement is significantly different in humans. These results are discussed with respect to the possible projections and functions of these neurons in humans.