Specific binding of [3H]paroxetine, a selective serotonin uptake inhibitor, has recently been described. We used the autoradiographic technique to establish the regional distribution of these binding sites in the brain of control and 5,7-dihydroxytryptamine (5,7-DHT) lesioned rats. Binding levels were highest in the dorsal raphe, followed by superior colliculus, thalamus, mammillary nuclei, ventral tegmental area and substantia nigra. Values were intermediate in hippocampus, hypothalamus, caudate nucleus and median raphe and lowest in the cerebral cortex and cerebellum. The degeneration of serotonergic terminals by 5,7-DHT completely prevented specific binding in the majority of brain regions analyzed, with the exceptions of raphe nuclei, ventral tegmental area and caudate nucleus. These data indicate that [3H]paroxetine binding sites are mainly localized on serotonin nerve terminals even if it seems that they cannot always be directly correlated to 5-HT uptake. © 1990.