Serotonin transport in synapses and platelets is inhibited by tricyclic antidepressants as well as by more selective transport inhibitors. This inhibition is hypothesized to be of importance for the psychotropic effect, although it is known that some new antidepressants do not possess this transport inhibitory action. We now report that antidepressive drugs can influence the serotonin transport complex in platelets and brain in other ways: [3H]imipramine and [3H]paroxetine, which bind with high affinity to the serotonin transport complex, can be dissociated from the complex with velocity constants strongly influenced by the different antidepressants. This effect is not correlated to the inhibitory action of the drugs on serotonin transport. Furthermore the effect is seen in the micromolar range in contrast to the high affinity binding process which takes place in the pico- and nanomolar range. The effects of antidepressants on the dissociation rates of bound ligand make it possible to differentiate between serotonin reuptake inhibitors which appear identical in other assays. Antidepressive drugs can thus be divided into groups which differ from the usual classifications.