The relationship of desipramine hydrochloride plasma concentration and antidepressant response was determined in 30 depressed inpatients treated for three weeks with desipramine. All patients had a nondelusional unipolar depression, met DSM-III criteria for major depressive episode with melancholia, and had a Hamilton score of 18 or greater after one week of hospitalization without medication. Eighty-nine percent of the patients with plasma concentrations above 115 ng/mL responded, in contrast to 14% of those with concentrations below this level, a significant difference (Fisher's exact test, P less than .001). Ten initial nonresponders were converted to responders when dosage increase raised desipramine plasma concentration to 125 ng/mL or above. In clinical practice a plasma concentration of 125 ng/mL would be a useful guideline as a threshold above which desipramine is likely to be effective.