Abnormalities in the neurohypophyseal system have been reported in depression. This study aimed to investigate serum oxytocin levels in patients with depression and the effects of gender and antidepressant treatment on these levels. Serum oxytocin levels were measured before and after treatment with antidepressant drugs or electroconvulsive therapy (ECT) in 40 inpatients (30 women, 10 men) who met the DSM-IV criteria for major depressive disorder (n=29) or bipolar affective disorder depressive episode (n=11), and in 32 healthy controls (20 women, 12 men). Serum oxytocin levels were decreased both pre-treatment and post-treatment in the patients compared with those in the controls. Serum oxytocin levels were not affected by antidepressant drug treatment or ECT. The female patients had significantly lower oxytocin levels than the control females, whereas no difference was found between the male patients and the male controls. We found no difference in serum levels of oxytocin between the unipolar and bipolar depressive patients. Our result shows reduced oxytocin in depression and a gender difference in oxytocin levels. Furthermore, antidepressant treatments appear to have no effect on serum oxytocin levels.