[3H]Paroxetine is a highly selective ligand for the 5-hydroxytryptamine transporter complex and the specific binding of this ligand to membrane fractions from cerebral cortex or hippocampus was studied in rats treated with specific inhibitors of the uptake of 5-hydroxytryptamine and monoamine oxidase inhibitors. The Kd and Bmax of the binding of [3H]paroxetine to cerebral cortical membranes of the rat was unaffected, compared to sham controls, by either acute or chronic administration with citalopram or chlorimipramine. Also, chronic treatment with chlorimipramine did not alter the parameters of the binding of [3H]paroxetine to hippocampal membranes from the rat compared to sham controls. Furthermore, chronic and acute treatments with clorgyline or deprenyl did not produce any significant changes in the Kd and Bmax of the binding of [3H]paroxetine to cerebral cortical membranes in the rat. These findings on the binding of [3H]paroxetine are discussed in light of previous equivocal results on the plasticity of neuronal binding sites for [3H]imipramine after various pharmacological treatments.