Inhibition of intercellular communication, as measured by metabolic cooperation between 6-thioguanine-sensitive and resistant Chinese hamster V79 cells, has been previously shown to be correlated with a large variety of known tumor promoters in many species and organ systems. The effects of anthralin and oleic acid, at non-cytotoxic concentrations, were shown to eliminate metabolic cooperation in Chinese hamster cells. Moreover, increased serum levels appear to reduce the effectiveness of 12-O-tetradecanoylphorbol-13-acetate, a powerful tumor promoter and inhibitor of metabolic cooperation, to eliminate metabolic cooperation. Results are consistent with the hypothesis that inhibition of metabolic cooperation is associated with an aspect of the complex tumor promotion process and indicate that in vitro culture conditions are critical for the proper assessment of potential tumor promoters.