The effect of fluoxetine on uptake of 5-hydroxytryptamine (5-HT) by enteric 5-hydroxytryptaminergic neurones has been analyzed in order to compare further these neurones with 5-HT neurones of the CNS. In addition, the effects of fluoxetine and chlorimipramine on efflux of [3H]-5-HT from the myenteric plexus were also evaluated. Fluoxetine was found to be a competitive inhibitor of 5-HT uptake by the myenteric plexus and was a more potent inhibitor of 5-HT uptake than was chlorimipramine. However, chlorimipramine enhanced the efflux of [3H]-5-HT more than could be explained by inhibition of 5-HT uptake and, therefore, appears to have the additional action of releasing the amine. These observations, similar to those of others studying central neurones, support the view that enteric 5-HT neurones resemble those of the CNS and are a useful model for the evaluation of drugs.