The pharmacological effects of monoamine potentiating antidepressants are likely to be expressed ultimately on cortical pyramidal neurones that use glutamate as a neurotransmitter. However, there are few data on the effects of antidepressant treatment on cortical glutamate levels in humans. The aim of the present study was to use proton magnetic resonance spectroscopy (MRS) to assess the effects of short-term administration of the selective serotonin re-uptake inhibitor, citalopram and the selective noradrenaline re-uptake inhibitor, reboxetine, on a composite measure of glutamate and glutamine (Glx) in occipital cortex in healthy volunteers using a parallel group, placebo-controlled design. We found that relative both to placebo and reboxetine, seven days treatment with citalopram significantly increased cortical Glx. Our data suggest that short-term treatment with citalopram, but not reboxetine, increases occipital Glx in healthy subjects. Further studies are needed to find out if similar effects occur in anterior brain regions and whether they reflect changes in glutamate or glutamine or both.