Imipramine (Tofrānil) therapy and artificial pyrexia obtained through the intravenous administration of typhoid vaccine in gradually increasing amounts were combined in the therapeutic management of special clinical problems encountered in depressed patients. Shortening of the time lag between the start of treatment and first significant improvement, a final favourable response in patients who at first had proved refractory to the drug and therapeutic control of acutely suicidal patients were the criteria for successful responses. These special criteria were met in 15 of our 28 patients (58%) subjected to pharmaco-fever therapy. It is assumed that the mechanism which contributed to a favourable response include the physiological lowering of the blood-brain barrier with a resulting increase of drug concentration in the target organ. On the psychological side, the unspecffic anxiety-reducing effects of pyrexia are noted as well as the facilitation of clinical and nursing management of acutely suicidal patients if they are confined to bed with a recurring fever of moderate degree.