Patients with depressive spectrum disorder (DSD) have low levels of the nor-epinephrine metabolite, MHPG. This study examines what happens to the low levels of MHPG following improvement of depressive symptoms. Sixteen depressed patients with a family history consistent with DSD showed no change in MHPG after 6 weeks of treatment. This was true for both treatment responders and nonresponders. The lack of change in low levels of MHPG suggests that reduced norepinephrine turnover is a biological trait of DSD patients. Implications of this finding are discussed.