Elimination of transformed fibroblasts through intercellular induction of apoptosis has been postulated as representing an efficient control step during oncogenesis. Whereas fibroblasts transformed by chemical carcinogens in vitro were sensitive to intercellular induction of apoptosis, ex vivo tumour cells derived from animals treated with chemical carcinogens were resistant to this control step. Resistance was achieved through two different mechanisms. Two cell lines overexpressed endogenous survival factors and thus the action of intercellular signalling (ICS) was not sufficient for complete depletion of endogenous survival factors. One of the resistant ex vivo tumour lines contained the same concentration of endogenous survival factors as its in vitro transformed and sensitive counterpart, but the endogenous survival factors were protected from the action of ICS in the resistant tumour cell line. In addition, the ex vivo tumour cell lines showed a marked independence of exogenous survival factors. Our data indicate that tumour formation requires independence of control by neighbouring cells and by exogenous survival factors.