Intercellular induction of apoptosis defines a potential control mechanism of oncogenesis. It is based on induction of apoptosis in transformed fibroblasts by neighboring nontransformed fibroblasts. Transforming growth factor type beta (TGF-beta) represents the initial triggering molecule to induce nontransformed cells to release apoptosis-inducing factors. To test whether sensitivity for intercellular induction of apoptosis is directly dependent on the transformed phenotype, v-src-transformed rat fibroblasts and emerging revertants were tested for their sensitivity. All transformed cell clones were sensitive, whereas all revertant clones had lost their sensitivity in parallel with the loss of the transformed phenotype. In addition, revertants had regained the potential to induce apoptosis in transformed cells. Sensitivity to intercellular induction of apoptosis is therefore directly dependent on the transformed phenotype, whereas the ability to induce apoptosis is a specific feature of nontransformed fibroblasts.