The uptake of free and bound ⁵⁷CoB₁₂, principally to transcobalamin II (TC II), was studied in isolated, perfused liver and kidney of the dog. (1) There was good uptake of canine TC II-B₁₂ by both organs. (2) In the liver TC II enhanced uptake over that of free B-12. (3) Renal uptake of free B-12 was greater than that of TC II-B₁₂. Free B-12 was neither lost in the urine nor returned to the circulation. (4) On a per gram tissue basis, renal uptake of TC II-B₁₂ was greater than hepatic. (5) There was renal release or production of TC II (6) Some TC II but more of a larger molecular size binder came from the liver. (7) Passing free B-12 through the kidney enhanced its uptake by the liver. (8) Passing free B-12 through the liver depressed its uptake by the kidney. (9) It is postulated that the distribution of B-12 can be modified by (a) different responses of tissue to TC II-B₁₂, (b) synthesis of TC II by an organ, and (c) the effects of B-12 passing through one organ to another.