Cortical glutamate/glutamine (Glx) metabolism seems to be affected by a major depressive disorder. Recently, a Glx deficit was detected by proton magnetic resonance spectroscopy (1H-MRS) in the bilateral anterior cingulum of depressives. The aim of this study was to assess the effect of successful electroconvulsive therapy (ECT) on Glx levels in the anterior cingulum. The left anterior cingulum of 17 severely depressed unipolar patients was measured by 1H STEAM spectroscopy before and after ECT, and the results were compared with those for 17 age- and gender-matched controls. We observed significantly reduced Glx levels in the patients' left cingulum compared to healthy controls. In ECT responders, in contrast to non-responders, Glx levels normalized (P=0.04) and then did not differ statistically from controls. Severe depression seems to be associated with a Glx deficit and increasing Glx may be an important mechanism of ECT action.