In the present study, we performed clinical trials of high-frequency rTMS (20Hz) for treatment of medication-resistant depression, and also examined the effect of rTMS on plasma levels of catecholamine metabolites and BDNF. Depressed 26 patients who met the DSM-IV criteria for major depressive disorder were enrolled to this study. All patients were administered left prefrontal 20 Hz rTMS at 80% MT over ten daily sessions, and plasma levels of MHPG.HVA and BDNF were measured before and after rTMS. As a result,the mean score of 20.5 (Ham-D) before rTMS significantly decreased to 15.6 after rTMS. The levels of plasma MHPG were significantly reduced after rTMS treatment. In addition, a negative correlation was observed between the change jn plasma MHPG levels and the change in scores of agitation. The plasma levels of BDNF significantly increased in responders and partial responders, but not in nonresponders, after rTMS treatment. These results suggest that rTMS treatment brings about some improvement in medication-resistant depression, especially for symptoms such as agitation, by influencing MHPG and BDNF. Furthermore, it should be emphasized that no patient enrolled in our study had severe side effects such as epilepsy. On the other hand, ECT, even though modified EOT, needs anesthesia, and is more often accompanied with amnesia than rTMS, This results suggest that rTMS is effective in major depressive disorder and rTMS is safety modality to treat depression.