1. The absorption of radioactive cobalamin was measured by a whole-body counting technique in control subjects and in patients with pernicious anaemia.
2. The absorption of cyanocobalamin by patients with pernicious anaemia was decreased by charcoal but not by bile or saliva.
3. The absorption of cyanocobalamin by control subjects was not affected by food but was significantly increased by pentagastrin. With pentagastrin the absorption of cyanocobalamin was significantly greater than that of hydroxocobalamin. The hog intrinsic factor-mediated absorption of cyanocobalamin by patients with pernicious anaemia was significantly depressed by pentagastrin.
4. The effect of increasing the mass of hog intrinsic factor concentrate on the absorption of cyanocobalamin by patients with pernicious anaemia could be described by a function relating the amount absorbed, the mass of intrinsic factor and two constants. The relationship implies that when the mass of intrinsic factor is small the amount of cyanocobalamin absorbed is directly proportional to the mass of intrinsic factor but that absorption approaches a saturation value with increasing mass of intrinsic factor. In physiological terms the function implies that absorption is proportional to the amount of cyanocobalamin attached to receptor sites but that cyanocobalamin attached to receptor sites may become detached and either reattached or lost to absorption.
5. With oral doses of 25 μg and 50 μg, control subjects absorbed more cyanocobalamin and hydroxocobalamin than patients with pernicious anaemia. At both dose levels control subjects absorbed more cyanocobalamin than hydroxocobalamin but no difference was observed in patients with pernicious anaemia. The intrinsic factor mechanism therefore influences amounts absorbed at such dose levels and appears to be a factor in the differences in absorption of cyanocobalamin and hydroxocobalamin.
6. The use of double-tracer techniques makes it possible for each subject to act as his own control in studies of vitamin B12 absorption. The value of this technique is stressed.