Extracellular interception of mutagens by excreted enzymes or by chemical agents that react with or bind to formed mutagens provides an important means of defense against chemical mutagens/carcinogens. Kada and Shimoi have classified molecules that function in this manner as "desmutagens," and many of them are natural cellular metabolites. Among the specific mechanisms that such agents may employ are: prevention of the activation of "promutagens" to mutagens; stimulation of enzymes (e.g., glutathione-S-transferase) that catalyze the binding/inactivation of damaging electrophiles; direct binding and concomitant inactivation of promutagens or mutagens; interference with uptake of mutagens into cells; etc. De Flora and Ramel have provided an excellent discussion of the mechanisms of these agents and a proposed classification scheme. Drawing on work from our own laboratories and other recent examples in the literature, several examples of mechanistic approaches to these studies using natural plant-derived materials, e.g., humic acid, Glycyrrhiza glabra extract, glutathione, and bioflavonoids, are also described. Antioxidants and agents that conjugate electrophiles will be among the modes of action described for obtaining the goal of intercepting mutagens/carcinogens.