1. 1. Values for the creatine content of whole blood have been determined for: (a) normal individuals, (b) patients suffering from various illnesses, (c) those with cyanosis or anemia, and (d) cases of cardiac failure before and after compensation. 2. 2. The elevation of creatine values in heart failure bore a relation to the degree of decompensation. Decreasing values indicated improvement, while stationary, high, or increasing values indicated severe cardiac failure, often impending death. On this basis serial levels may be of prognostic value. 3. 3. Fatigue, an important early symptom of impending cardiac decompensation, may be due to a decrease of elements essential to muscle contraction, of which creatine is one. The values of biopsied muscle creatine showed a similar but opposite variation to those observed in blood, i.e., cardiac failure is accompanied by increase of creatine in the blood and decrease in the muscle. With return of compensation, this relationship is reversed. Vitamin E caused an increase of muscle creatine above that resulting from compensation only.