Persistent deficiency of serum B12-binding alpha-1 globulin was demonstrated in two brothers, manifesting primarily as low serum B12 levels. Despite the inability of one subject to maintain normal levels of B12 in the blood, as shown by persistently low serum values despite monthly injections of B12, no evidence of metabolic B12 deficiency could be found. Tissue B12-storing ability appeared to be intact. His brother exhibited only minimal hypersegmentation of neutrophil nuclei; otherwise, he too presented a completely normal picture. The normally present alpha globulin B12-binder was virtually absent from saliva and peripheral leukocyte extracts of both subjects. Current indirect evidence favors neutrophils as at least a partial source of the serum globulin.33 The cause of the possibly hereditary defect in the 2 subjects is unknown. Neither excessive B12-binding protein excretion34 nor a destructive factor in their serum or leukocytes was found.