It was observed that the subcutaneous injection of Russell's Viper venom initiated an explosive release of heparin-containing granules from local tissue mast cells and that the shed granules were subsequently ingested by fibroblasts and various other cell types involved in the connective tissue response to venom injury. Investigations of the significance of these cellular events indicated that heparin can form acid-base complexes with noxious factors of the venom in vitro and inhibit both local and systemic injury by this venom in mice. Inasmuch as this antivenom effect of heparin is only one aspect of a more general antitoxic activity of this mucopolysaccharide, it is suggested that the degranulation of mast cells may serve an important function in local resistance to injury by various cationic substances.