In order to investigate further the role of gap-junctional intercellular communication in the process of cell transformation, we examined the effects of chemicals that modulate gap-junctional communication on the induction and maintenance of transformed foci in BALB/c 3T3 cells. When dibutyryl cyclic AMP, retinoic acid, fluocinolone acetonide, or dexamethasone was added during the induction of cell transformation by standard (3-methylcholanthrene alone) or two-stage (low dose of 3-methylcholanthrene plus phorbol ester) protocols, there was a significant decrease in the number of transformed foci. When BALB/c 3T3 cells are transformed, there is selective intercellular communication between transformed and between surrounding nontransformed cells: transformed cells communicate among themselves but not with surrounding normal cells. Addition of dibutyryl cyclic AMP, retinoic acid, fluocinolone acetonide, or dexamethasone to culture dishes in which transformed foci were present induced communication between transformed cells and surrounding normal cells. In the continuous presence of these chemicals, there was a clear decrease in the number of transformed foci. These chemicals therefore appear capable of reestablishing intercellular communication between transformed and nontransformed cells and of diminishing the number of transformed foci. However, when transformed cells were isolated and placed in culture dishes at clonal density in the presence of these chemicals, there was hardly any decrease in the number of transformed colonies, suggesting that the chemicals cannot revert the phenotype of transformed cells in the absence of normal cells. These results suggest that chemicals that modulate intercellular communication not only inhibit the induction of transformed foci but also revert transformed cells to the normal phenotypes by establishing intercellular communication with surrounding normal cells.