Summary1. A short-term dialysis procedure has been developed for studying cobalamin-protein reactions. 2. Aquocobalamin (vit. B12b) was much more reactive than cyanocobalamin, being bound in rather large amounts by several protein preparations of diverse origin. In several instances binding was increased by denaturation and decreased in acid media. It is suggested that this type of binding may occur via cobalichrome formation. 3. A gastric mucosal extract bound large and equal amounts of aquocobalamin and cyanocobalamin, apparently at the same binding site. Excess cyanide has no effect on the cyanocobalamin-gastric extract reaction in neutral media, but exhibits an inhibiting effect at high pH levels. In this reaction the cyano-group of cyanocobalamin is not released, but remains in a photolabile position. It is suggested that the cobalt atom participates in the reaction and that it is the position occupied by the substituted benzimi-dazole moiety that is involved.