This paper defines selective and nonselective apoptosis induction in transformed and nontransformed fibroblasts by extracellular reactive oxygen and nitrogen species (ROS and RNS). Superoxide anions do not exhibit direct apoptosis inducing potential, whereas their dismutation product hydrogen peroxide induces apoptosis nonselectively in transformed and nontransformed fibroblasts. Myeloperoxidase converts hydrogen peroxide into the selective apoptosis mediator HOCl, which interacts with transformed target cell-derived superoxide anions and generates apoptosis-inducing hydroxyl radicals. Nitric oxide does not induce apoptosis directly in fibroblasts. However, interaction of nitric oxide with transformed cell-derived superoxide anions leads to the generation of the ultimate apoptosis inducer, peroxynitrite. Peroxynitrite by itself does not discriminate between transformed and nontransformed cells. The direction of generation of apoptosis inducing ROS and RNS to the site of superoxide anion production has relevance for the selectivity of ROS and RNS-based natural antitumor systems, as extracellular superoxide anion generation represents a hallmark of the transformed state.