Protryptiline, a new antidepressant, was evaluated in a double-blind study. Results were compared with those obtained in similar groups of patients treated with imipramine and amitryptiline. After full psychiatric and medical assessment, patients were rated on a "target-symptom" scale, were assessed weekly and underwent a number of tests before and after treatment, including a hemogram and estimations of serum bilirubin, cephalin flocculation and serum protein values. Observations were made over four to six weeks. The starting dosage was 10 mg. protryptiline three times daily with a maximum of 60 mg. daily. Beneficial responses occurred in 13 of 20 patients (65%). Protryptiline-treated patients had the earliest response to drug treatment, 11 showing some improvement within the first week. Twelve patients (60%) had side effects, mainly minor, indicative of anticholinergic activity. One developed leukopenia which was reversible, and one showed increased excitement; in both, therapy was discontinued. Protryptiline gave clinical results that compared favourably with those of antidepressants of established value. While toxic effects should be carefully watched for, further trials are warranted to decide whether protryptiline possesses special or new advantages in psychopharmacotherapy.