BACKGROUND: Studies suggest that the dorsolateral prefrontal cortex (DLPFC) participates in neural circuitry that is dysregulated in Panic Disorder (PD) and Major Depressive Disorder (MDD). We tested whether low-frequency repetitive Transcranial Magnetic Stimulation (rTMS) could normalize the overactivity of right frontal regions and thereby improve symptoms. METHODS: Six patients with PD and comorbid MDD were treated with daily active 1-Hz rTMS to the right DLPFC for 2 weeks in this open-label trial. RESULTS: Clinical improvements were apparent as early as the first week of treatment. After the second week, 5/6 of patients showed improvements in panic and anxiety, and 4/6 showed a decrease in depression, with sustained improvement at 6 months of follow-up. Right hemisphere resting motor threshold increased significantly after rTMS. LIMITATIONS: Limitations of this study are the open design and the small sample size. CONCLUSIONS: Slow rTMS to the right DLPFC resulted in significant clinical improvement and reduction of ipsilateral motor cortex excitability. Replications in larger sample will help to clarify the relevance of this preliminary data and to define the potential role of right DLPFC rTMS in panic with major depression.