In a group of patients suffering from manic depressive illness treated with lithium carbonate occasional large increases in creatine phosphokinase (C.P.K.) activity were seen. These were found to occur at times when the patients were stable in mood and clinically well. The serum lithium levels were adequate in all cases at the time of raised C.P.K. activity. Raised C.P.K. activity can be an indication that the disease is active but is controlled by lithium.