BACKGROUND: Elevated arginine vasopressin (AVP) plasma levels have been observed in major depression, particularly in relation to the melancholic subtype. Two hypothalamic structures produce plasma vasopressin: the supraoptic nucleus (SON) and the paraventricular nucleus (PVN). The aim of this study was to establish which structure is responsible for the increased vasopressin plasma levels in depression. METHODS: Using in situ hybridization, we determined the amount of vasopressin messenger ribonucleic acid (mRNA) in the PVN and SON in postmortem brain tissue of nine depressed subjects (six with the melancholic subtype) and eight control subjects. RESULTS: In the SON, a 60% increase of vasopressin mRNA expression was found in depressed compared with control subjects. In the melancholic subgroup, AVP mRNA expression was significantly increased in both the SON and the PVN compared with control subjects. CONCLUSIONS: We found increased AVP gene expression in the SON in depressed subjects. This might partly explain the observed increased vasopressin levels in depression.