Some symptoms of posttraumatic stress disorder (PTSD) are related to central nervous system adrenergic hyperarousal. It has been suggested that an adrenergic receptor-blocker could be used to diminish, if not alleviate, the target symptoms of PTSD. Severely traumatized Cambodian refugee patients (N = 68) who suffered from chronic PTSD and major depression improved symptomatically when treated with a combination of clonidine and imipramine. A prospective pilot study of nine patients using this combination of an alpha-2 adrenergic agonist and a tricyclic antidepressant resulted in improved symptoms of depression in six patients, five to the point that DSM-III-R diagnoses were no longer met. The average decrease in the Hamilton Rating Scale for Depression score was 16. PTSD global symptoms improved in six patients but only in two to the point that DSM-III-R diagnoses were not met. There was no further sleep disorder in five and the frequency of nightmares lessened in seven patients. Startle reaction improved only in four patients; avoidance behavior showed little improvement in any of the nine. The imipramine-clonidine combination was well tolerated and presents a promising treatment for severely depressed and traumatized patients, although further studies are needed.