Twenty-three patients with major depressive disorder were treated with bupropion in an open-design protocol. Fifteen (65.2%) of the 23 responded with a more than 50% decrease in scores on the Beck Depression Inventory. Patients with trough blood levels of 10-29 ng/ml had a significantly better response than those with trough levels of 30 ng/ml or more. This preliminary result warrants further, double-blind evaluation.