In 1925 COOLEY and LEE€ or the first time clearly defined as a distinct clinical entity a chronic, progressive, and fatal anemia of childhood which is characterized hematologically by hypochromia, micro-, aniso-, and poikilocytosis, decreased erythrocyte fragility in hypotonic saline solutions, peripheral erythroblastosis, failure to respond to any known anti-anemic therapy, and an increased incidence of oval and “target” red blood cells. These latter are erythrocytes which on stained smears instead of the usual achromic center appear to have a central dot and peripheral ring of hemoglobin separsted by an intervening zone of pallor. Some fifteen years later WINTROBE, MATHEWS, POLLACK and DOBYNS (1940), DAMESHEK (1940), and STRAUSS, DALAND, and Fox (1941) independently described an anemia qualitatively similar to that described by COOLEY and LEE but quantitatively very much less severe, never terminating fatally. Both anemias were found to be familial, and confined in large part to the socalled Mediterranean peoples-Italians, Greeks, Turks, Cypriots, etc., and their descendants. Although ANGELINI (1937, quoted from WINTROBE et al., 1940) and CAMINOPETROS(1938) had observed fragility changes in the blood of parents of patients with the severe anemia described by COOLEY and LEE, it remained for WINTROBF (1942) and SMITH (1942) to point out that the above mentioned mild anemia was present in the parents and some of the siblings of children with COOLEY’S anemia. This finding has been confirmed by DAMESHEK (1943), SMITH (1943), and VALENTINE and

Three theories regarding the inheritance and relationship of these two anemias have been advanced, namely,(I) that the severe disease is due to homozygosity for an inherited factor which when heterozygous produces the mild condition, an hypothesis adumbrated by CAMINOPETROS(1938), and advanced later by DAMESHEK (1943)~(2) that both anemias are due to a variably expressed dominant (SMITH, 1g43), and (3) that the severe anemia is due to the interaction of two non-allelic dominant factors (MCINTOSH and WOOD, 1942). This latter theory was presented at a time when the only recognized abnormality in the blood of parents of patients with the severe disease was the fragility change (CAMINOPETROS, 1938); it was suggested that