AbstractThe efflux of3H‐5‐HT from a crude synaptosome preparation of the cerebral cortex of reserpinized rats was examined. The synaptosomes were loaded with3H‐5‐HT by pre‐incubation of the homogenate in presence of pargyline and desipramine in order to inhibit deamination of 5‐HT and uptake into noradrenergic neurones. The synaptosomes were collected by centrifugation, washed and resuspended in 0.25 M sucrose. No spontaneous efflux of 5‐HT was detectable at 0°C but marked efflux was observed at 27°C and 37°C. 4‐Chloroamphetamine, low external Na+concentration, ouabain and the depolarizing agent veratridine markedly accelerated the initial (5 min) efflux. Inhibitors of the neuronal 5‐HT uptake,e.g.chlorimipramine, H 102/09 and A 23189, antagonized the 5‐HT efflux evoked by these means, whereas desipramine, which is a poor inhibitor of the 5‐HT uptake, had only slight effect on the 5‐HT efflux. It is suggested that 5‐HT can be actively transported out from the synaptosomes by the re