Dopamine (DA) has been suggested as the penultimate agent in the neurotoxic effects of methamphetamine on serotonergic neurons. DA increases the efflux of tritium from rat neostriatal slices preloaded with [³H]serotonin in a concentration-dependent manner. This serotonin (5-HT) release is inhibited by the same selective uptake blockers previously shown to protect serotonergic neurons from the neurotoxic effects of methamphetamine in vivo. The results indicate that the 5-HT uptake carrier transports DA into the serotonergic neuron by a heteroexchange process with 5-HT. This further suggests that the excessive DA release induced by methamphetamine in vivo could lead to the uptake of DA into serotonergic neurons.