Sudden failure of an occasional patient afflicted with Addison-Biermer's disease (Addisonian pernicious anemia) to respond to adequate amounts of purified liver extracts in the absence of factors known to interfere with a therapeutic response has been observed by us during the past few years in the Minneapolis General Hospital. The occurrence of a refractory state for no apparent reasons has also been noted by others (1 to 4). Because little is known about the chemical nature of the liver factor (anti-pernicious anemia factor) or the physiologic dose, including the development of a progressive anemic state under adequate amounts of purified liver extracts, we felt justified in publishing an observation which we believe may indicate one of the mechanisms responsible for a sudden refractory behavior of certain patients. We could demonstrate in a male afflicted with Addisonian pernicious anemia that fatty liver and fatty metamorphosis of the bone marrow organ were apparently factors in the development of a progressive anemic state.Without further administration of liver extract, the progressive anemic state was brought into remission by means of the administration of a 5 per cent solution of choline chloride (Merck), 20 ml. intravenously for 16 successive days. The doses were given at a rate of 1 ml. per minute.The first dose caused flushing and some nausea after 10 ml. were administered. No significant drop in blood pressure was observed. The successive doses were well tolerated. CASE HISTORYThe patient, a male, who -for several years responded in a characteristic manner to the administration of liver extracts intramuscularly and maintained a normal peripheral blood status on 3 ml. monthly of fairly crude liver extracts containing about % to 2 U.S.P. units per ml., developed a progressive anemic state when purified liver extracts were substituted containing about 10 and 15 U.S.P. units