Summary Human gastric juice contains small amounts of vitamin B12 or its equivalent as assayed by L. lactis. Crystalline vitamin B12 was added to gastric juice and the solutions were incubated at pH 2, 3 and 7; there were no observed changes in the absorption spectra or in the microbiological activity over a 22-hour period. Again, crystalline vitamin B12 was added to gastric juice, and after incubation at pH 2 and 7 at 37°, much of the vitamin B12 was recovered. No evidence was found for a chemical reaction between vitamin B12 and the intrinsic factor which results in a gross structural change in vitamin B12. A possible reaction between vitamin B12 and the intrinsic factor in which there was a very small structural change of the large vitamin B12 molecule, and which could produce as little as 5 μg of orally active product is being investigated. A concentrate prepared from beef muscle having vitamin B12-like microbiological activity was found to be hematopoietically active when administered by the parenteral route to pernicious anemia patients; thus, the extrinsic factor acts like vitamin B12. These results support the previously derived hypothesis that the effect of the intrinsic factor is due to its ability to promote the absorption of the small amounts of vitamin B12 or its equivalent which occur in natural foods. The mechanism of this enhancement is being studied further.