By L. S. P. DAvIDsoN, BA., M.D., F.R.C.P.ED. AND LOND., F.R.S.ED. T HE TERM ‘ ‘refractory anemia’ ‘ was introduced by Bomford and Rhoads ( 1941) for anemias of a wide variety of types that were refractory either temporarily or permanently to hematinic therapy. In 1943 Davidson, Davis and Innes published a series of papers entitled ‘ ‘Studies in Refractory Anaemia’ ‘ which dealt with the problem of classification on the basis of examination of the bone marrow by sternal puncture and divided the anemias refractory to liver extracts into two main groups, namely (i) refractory anemias with hypocellular normoblastic marrows, and (i) refractory anemias with hypercullular megaloblastic marrows. Of particular significance was their finding that the prognosis was vastly different in the two groups. Thus, of i6 patients in Group i, ii died of progressive anemia within a few months, while of i6 cases in Group i all eventually made a complete recovery. Intensive treatment with large amounts of liver extract supplemented with iron and vitamins and repeated blood transfusions was required for long periods if such satisfactory results were to be obtained. The long period of illness during which life was continuously in danger indicated the need for some therapeutic agent which would cause a prompt remission comparable to that obtained with parenteral liver therapy in the relapse stage of Addisonian pernicious anemia. In this paper the term refractory megaloblastic anemia is confined to cases of megaloblastic anemia which failed to respond hematologically and clinically to the parenteral administration of an amount of liver extract which has been proved to produce an optimal response in cases of Addisonian pernicious anemia. The test preparation employed was Anahaemin, marketed by British Drug Houses Ltd., which has been found by the writer to be potent in a dose of i cc. when administered parenterally in a large number of cases studied during the past ten years. Every patient with refractory megaloblastic anemia received at least twice this dose after admission to hospital. In addition many cases had received large amounts of potent liver extracts prior to being referred to us for investigation of their failure to respond. Since infections, intoxications and advanced arteriosclerosis are known to inhibit or delay the response to parenteral liver therapy, patients exhibiting any of these complications were not included in the group of refractory megaloblastic anemia discussed below. For many years the writer has suggested that chemical purification of liver extracts for parenteral use removes some essential factor which is necessary for the restoration of normal blood formation in certain cases of megaloblastic anemia which have failed to respond to potent liver extract given parenterally. The following case history of a patient seen by the writer nearly fifteen years ago illustrates this problem very clearly.