Twenty-two depressed adults were scanned with perfusion single-photon computed emission tomography before and after 2 weeks of left perfrontal transcranial magnetic stimulation (TMS) in a parallel design, double-blind treatment study. At medication-free baseline, across all subjects, blood flow in the bilateral medial temporal lobes, left prefrontal cortex, and caudate significantly declined with increased depression severity. Also at baseline, depressed adults who responded to TMS, compared with nonresponders, showed increased inferior frontal lobe activity. Following treatment, there was an even greater difference in inferior frontal blood flow in responders compared with nonresponders, and the negative baseline correlations between depression severity and limbic and prefrontal blood flow disappeared. These results suggest that in depressed adults, 10 days of prefrontal TMS affects prefrontal and paralimbic activity, which may explain its antidepressant effects.