FATIGUE is one of the most interesting topics of conversation among physicians and nurses but, as is so true of many medical expressions, the exact meaning of the word "fatigue" is vague and indefinite. There are, of course, a great many ways of defining it. Fatigue should mean not the impairment of one's ability to function which comes after unusual or prolonged physical exertion, but rather the total inability to manifest interest, enthusiasm, concentration, and so on that is so commonly seen after prolonged combinations of physical and emotional distress. Physicians see patients with this problem of fatigue much more commonly than most people realize. It is not unusual for a physician to find that at least two out of every three of his office patients have it. Admittedly, a patient does not always say, "Doctor, I am coming to you because I am fatigued." More often the diagnosis is arrived at only after laborious and extensive examinations involving many types of tests. Examinations of this kind, which have been carried on at the University of Oregon Medical School by the Department of Psychiatry and the Department of Chemistry together, have revealed some very interesting things about the fatigue syndrome. The results of these experiments and our own observations make us feel that we are a little closer to truly understanding what the subject of fatigue covers.