The research to be performed in the Hematology Research Laboratory of the Massachusetts General Hospital is concerned with: (1) studies of the optimal methodology for the assay of serum vitamin B12 and its naturally-occurring analogues; (2) isolation and chemical identification of the cogalamin analogues in serum and tissues; (3) studies of the capacity of analogues to be converted enzymatically to 5'-deoxyadenosyl and methyl derivatives and of the capacity of these derivatives to serve as coenzymes of cobalamin-dependent enzymes; (4) studies of the source(s) and metabolic fate of cobalamin analogues; (5) systematic evaluations of the clinical and pathophysiologic significance of serum cobalamin analogues.