We studied the differential response of oncogene transformed NIH3T3 cells to glucocorticoids. As demonstrated for transformed human fibroblasts, the morphology of neu-, ras-, src- and sis-transformed mouse fibroblasts became more normal after glucocorticoid treatment. This change was not due to inhibition of the expression of oncogene mRNA or protein. However, the abl-transformed NIH3T3 cells were resistant to glucocorticoid-induced morphology change. These results indicate that the glucocorticoid-induced morphology change is specific to certain oncogene-transformed NIH3T3 cells. Transformed human fibroblasts generally have reduced amounts of cell surface fibronectin. When treated with glucocorticoids, they incorporate higher levels of fibronectin in their extracellular matrix, which correlates with their change in morphology. However, we found that, except for abl-transformed cells, the fibronectin level of the other oncogene transformed mouse cells was similar to non-transformed cells. Moreover, treatment of the neu-, ras-, src- and sis-transformed cells with glucocorticoids resulted in a change in morphology but no increase in cell surface fibronectin. These studies demonstrate that the glucocorticoid-induced morphological change of oncogene-transformed NIH3T3 cells is not due to enhanced expression of fibronectin. Therefore, other mechanisms are responsible for this glucocorticoid-induced phenotypic change of oncogene-transformed cells.