The dissociation rates of [3H]nisoxetine, [3H]GBR 12935 and [3H]citalopram from, respectively, the rat brain noradrenaline, dopamine and 5-HT transporters were found to be markedly affected by several drugs. Sertraline strongly attenuated the rate of dissociation of [3H]nisoxetine from the noradrenaline transporter, while citalopram strongly attenuated that of [3H]citalopram from the 5-HT transporter. The effect of both drugs were stereospecific. Less potent affinity-modulating drugs were identified with regards to [3H]GBR 12935 dissociation from the dopamine transporter. All three neuronal monoamine transporters may thus have specific affinity-modulating sites which change the function of the transporters with possible implication for the reuptake of monoamines released during synaptic activity.