Background: Serotonin transporters (SERT) are a major target for antidepressant medication, although there have been limited in vivo studies of SERT availability in patients being treated with antidepressants. it is not known whether SERT availability differs in treatment-responsive and -nonresponsive patients receiving long-term treatment. In this study, we used single photon emission computed tomography (SPECT) to compare SERT residual availability in unipolar responders and nonresponders during long-term antidepressant treatment. Dopamine transporter (DAT) availability was also assessed in The same patients to examine the relationship between the two transporter systems. Methods: Twenty-four medicated unipolar patients were recruited, of whom 11 were responders and 13 were nonresponders. All patients underwent SPECT with [I-123]-beta-carbomethoxy-3-beta-(4 iodophenyl)tropane, Brain SERT was measured in the brain stem and diencephalon, and DAT was measured in the striatum. Residual availability was calculated as a ratio of specific to nonspecific uptake, with the occipital region used as the nonspecific reference region. Results: There was no difference between responders and nonresponders in SERT availability. Dopamine transporter availability was similar in responders and nonresponders, and there was no association between SERT and DAT availability. Conclusions: Serotonin transporter availability does not discriminate responders and nonresponders during long-term. treatment with antidepressants.