Repetitive transcranial magnetic stimulation (rTMS) has antidepressant effects in patients with major depressive disorder. The mechanisms of action and optimal stimulation parameters remain unclear. To test the hypothesis that rTMS exerts antidepressant effects either by enhancing left dorsolateral prefrontal cortex (DLPFC) excitability or by decreasing right DLPFC excitability, the authors studied 45 patients with unipolar recurrent major depressive disorder in a double-blind, randomized, parallel group, sham-controlled trial. Patients were randomized to receive 1 Hz or 10 Hz rTMS to the left DLPFC, 1 Hz to the right DLPFC or sham TMS. Left 10 Hz and right 1 Hz rTMS showed similar significant antidepressant effects. Other parameters led to no significant antidepressant effects.