The monoamine oxidase A (MAO-A) has been suggested to be involved in the pathogenesis as well as the pharmacological treatment of Major Depression. In the present study, 340 patients with a Major Depressive Episode (f=194, m=146; DSM-IV) of Caucasian descent were genotyped for the functional MAO-A VNTR. The clinical response to antidepressive pharmacological treatment was assessed by weekly intra-individual changes of HAM-D-21 scores over six weeks. The longer MAO-A alleles (3a, 4, 5) conferred a significant risk of slower and less efficient overall response over the course of 6 weeks of antidepressant treatment in patients with Major Depression, with the effect being restricted to female patients (p=0.028; corrected for multiple testing). The present results suggest that high-activity MAO-A genotypes possibly by consecutively decreased serotonin and/or norepinephrine availability negatively influence antidepressant treatment response during the first six weeks of pharmacological treatment in female patients with Major Depression.