Intestinal absorption of 14CH3- and/or 57Co-methylcobalamin (CH3-B12) was studied with regard to chemical changes. It was found that absorption of a physiologic dose of CH3-B12-57Co in the rat was the same as that of cyanocobalamin (CN-B12) in quantity and speed, but more radioactivity accumulated in liver after 8 hours, indicating a gradual conversion of CH3-B12 to hydroxocobalamin and cobamide coenzyme. Schilling test with CH3-B12-57Co yielded urinary excretion about 1 3 that with CN-B12-57Co, and similar changes of CH3-B12 in human body were suggested. In the rat, expiration of 14CO2 following oral administration of 14CH3-B12 was small, as contrasted by quick and massive evolution of 14CO2 when photolyzed 14CH3-B12 was given. With supraphysiologic doses, more than 60 per cent of 14C disappeared from the gastrointestinal tract in 2 to 3 hours, suggesting instability of free CH3-B12, and there was a distinct difference in tissue distribution between 14C and 57Co following administration of 14CH3-B12-57Co. It seems, therefore, that cleavage of -CH3 in vivo is different in mechanism from that in vitro or after photolysis. Paper chromatography of digested ileal mucosa obtained after oral administration of a small dose of CH3-B12-57Co, demonstrated unchanged CH3-B12 and some other cobamides. It is concluded that in the alimentary tract, free CH3-B12 is labile and loses CH3 progressively. However, in a physiologic situation where intrinsic factor is operative, CH3-B12 may be partially protected by it from such chemical changes.