Pathogenetic prinicples of pernicious anemia are studied by labeling marrow cells of a patient in vitro with DNA and predominant RNA precursors. Results with H3-thymidine confirm that megaloblasts proliferate intensively in the basophilic and polychromatophilic stages. High rates of incorporation were also obtained for H3-uridine and H3-cytidine, especially in immature cells. In pernicious anemia the aberrant megaloblastic erythropoiesis apparently utilizes uridine and cytidine abundantly in spite of the metabolic block postulated for thymidylic acid synthesis. This study supports previous findings that RNA synthesis is active and not affected by B12 deficiency. Homoplastic cell divisions and inhibition of nuclear maturation seems to be characteristic features of megalo-blastosis, leading clinically to severe anemia and increased erythro-cyte hemolysis. Red cell destruction apparently occurs partially within the marrow with inefficient erythropoiesis and low rate of Fe59 incorporation and partially in the peripheral blood with shortened survival and increased red cell iron turnover rate.