The effect of environmental and genetic parameters on cell death was studied in Chinese hamster ovary cell cultures. Experiments were performed using an anchorage-dependent CHO cell line expressing gamma -IFN, and a second cell line obtained by transfection of the previous one with bcl-2. In serum-free medium the two cell lines showed a considerable degree of growth control entering quiescence while maintaining high viabilities. The addition of transferrin did not have any effect but insulin addition allowed cells arrested by serum withdrawal to reenter the cell cycle. However, insulin supplementation also resulted in cell death, which was possible to avoid through bcl-2 overexpression or in the presence of serum. We propose that the expression of c-myc, shown to be induced by insulin, plays an important role in the cell death observed after insulin addition in an inappropriate environment, deficient in protective factors. This hypothesis is supported by measurements of c-myc expression and cell cycle distribution.