Previous studies have shown that the chemically transformed AKR-MCA and C3H/MCA-58 cell lines spontaneously arrested growth at high saturation density in the G1 phase of the cell cycle because of depletion of low-molecular-weight nutrients (amino acids and glucose) from the medium. The nontransformed parent cell lines, AKR-2B and C3H/10T1/2, spontaneously arrest growth in G1 at low saturation density because of depletion of essential serum growth factors. If prevented from becoming deficient in growth factor by maintenance in medium with mitogens such as epidermal growth factor (EGF), fibroblast growth factor, or the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, the nontransformed AKR-2B cells behave similarly to the transformed cells and arrest growth in G1 at high saturation density because of nutrient deficiency. This suggests that a major difference between the nontransformed and chemically transformed cells is an inability of the latter to achieve growth factor deficiency. In addition, the transformed AKR-MCA and C3H/MCA-58 cells show greatly diminished detectable EGF receptors. These observations could be accounted for by the endogenous production of the response to a growth factor-like substance by the transformed cells. Preliminary data indicate that these chemically transformed cells release a transforming growth factor (TGF) into serum-free medium. Whether TGF is similar or identical to the previously described sarcoma growth factor remains to be established.