Six patients with the diagnosis of acute mania were treated with high doses of the beta-adrenergic blocking agent propranolol. One of these patients was treated during two manic phases. Psychopathologic change during treatment was rated daily by a psychiatrist not informed on the patients medication. The IMPS (Inpatient Multidimensional Psychiatric Scale) was used. Three cases were placebo-controlled under double blind conditions. Four times we had a second medication period, twice with propranolol and once with oxprenolol and dexpropranolol respectively. Propranolol was administered every 4 h (six times per day), starting with single doses of 20-40 mg. Doses were increased individually under control of pulse rate, blood pressure, and ECG. Augmentation of doses was continued until an effect on manic symptomatology was undoubtedly seen or until therapy had to be discontinued because of side-effects. In four patients definite improvement of manic symptomatology could be achieved during altogether five manic phases within usually two treatment periods of 5-15 days. Manic behavior disappeared completely in two of these patients. The effective dosage of propranolol varied between 280 and 2320 mg per day. All of the improved patients relapsed after discontinuation of the drug. In the only case on dexpropranolol (5 days up to 900 mg daily) the effect was questionable. No extrapyramidal side-effects were observed. In one patient treatment was discontinued because of lack of cooperation, in another because of extrasystoles. Gastrointestinal bleeding occurred in the patient who received dexpropranolol. This complication was possibly due to other medication. Other side-effects were insomnia, hypertension, precordial pain, abdominal pain as well as the expected hypotension and bradycardia. The significance of these results regarding the catecholamine hypothesis of manic-depressive illness is discussed.