1. Electrophoretic mobility of brain-type creatine phosphokinase (CPK) from rabbit, rat and human decreased after incubation in human plasma for 3 h or 17 h but did not change after incubation in isotonic saline solution. The presence of the reducing agent mercaptoethanol during incubation in human plasma tended to reduce the rate of change of electrophoretic mobility of BB-CPK. 2. The activity of brain CPK was almost completely lost after incubation for 17 h in human plasma. The addition of mercaptoethanol after incubation of brain CPK in human plasma could only partially restore the enzyme activity. 3. The decrease in electrophoretic mobility of rat brain CPK occurred after incubation in an ultra-filtrate of human plasma which contained molecules whose molecular weight did not exceed 1000. 4. Gel chromatography indicated that incubation of brain CPK in human plasma did not markedly change the molecular size of the enzyme.