Paroxetine is the most potent and one of the most specific serotonin uptake inhibitors. High-affinity 3H-paroxetine and 3H-imipramine binding was compared in rat neuronal membranes. The KD value for 3H-paroxetine binding to neuronal membranes was 0.08 nM, which is exactly the same value as with platelet membranes. The KD value for 3H-imipramine binding to neuronal membranes was about 4 nM, which is higher than the KD value for 3H-imipramine binding to platelet membranes (0.5 nM). The results indicated that the 3H-paroxetine binding site is identical in neuronal membranes and in platelet membranes; this binding site is probably located on the serotonin transport mechanism. In addition, part of the high-affinity 3H-imipramine binding to neuronal membranes is probably located on the serotonin transport mechanism, but another part is located elsewhere. Furthermore the polypeptides containing the 3H-imipramine binding sites may not be identical in neuronal and platelet membranes.