Transcobalamins are proteins which carry vitamin B12 and which are normally partly unsaturated. This study of transcobalamins was carried out in 17 subjects with megaloblastic anemia (12 true cases of pernicious anemia and 5 cases of folate deficiency). Among the latter, the transcobalamins were studied in 4 cases of pernicious anemia, before and after treatment with vitamin B12. The distribution of endogenous B12 was determined in four normal controls and two cases of pernicious anemia. This vitamin is normally distributed roughly equally between the three transcobalamins, whereas in B12 deficiency, T.C.2 is very unsaturated together with T.C.1 to a lesser degree. The latent fixation capacity of the serum is increased together with the latent fixation capacity of T.C. I and, above all, T.C. II but that of T.C. III is reduced in patients with pernicious anemia. In folate deficiency, only the latent fixation capacity of T.C. II is increased. When vitamin B12 is administered in physiological dosage, T.C. I becomes gradually saturated. In pharmacological dosage, total fixation capacity together with that of T.C. I and T.C. II become gradually reduced, but in spite of high levels of circulating B12, these proteins remain partially unsaturated. Various theories are suggested to explain the variations of these three transcobalamins in megaloblastic anemia but the problem is still unclear.