The solubility of decalcified bone collagen was studied in various salts and nonelectrolytes. It was found that collagen was extracted as gelatin at low temperature and at near neutral pH by a number of salts known to promote the conversion of collagen to gelatin. Successive extractions by such reagents dissolved essentially all the bone collagen. The extracted gelatins representing ~ 80per thousand of the total amount of collagen present in the bone, consisted predominantly of a component having the characteristics of the single stranded x-chains. It was concluded that the stability to dissolution of the collagen in the native bone tissue in solvents such as cold NaCl or dilute acetic acid is due primarily to the way in which the collagen macromolecules interact in the fibrils. In contrast to the protein mediated solvent-solvent interactions which are thought to play a major role in stabilizing the three polypeptide chains in the collagen helical configuration, the intermolecular interactions are influenced primarily by stereochemical factors that control direct protein-protein interactions.