The transcription of the rat alpha 2u globulin gene family is under complex hormonal control, involving the participation of glucocorticoids, estrogens, insulin, and growth hormone. The glucocorticoid induction of alpha 2u globulin is a secondary response; that is, ongoing protein synthesis is necessary for induction of alpha 2u globulin mRNA by the hormone. This secondary response is maintained when alpha 2u globulin genes are transfected into tissue culture cells which contain the glucocorticoid receptor. We have found that the glucocorticoid induction of alpha 2u globulin occurs only in permanent cell lines, in which the alpha 2u globulin genes are integrated into the host cell DNA; induction in transient transfections is minimal. Further, the DNA sequences required for alpha 2u globulin secondary response lie entirely in the 5' proximal promoter region; no intragenic sequence elements are required for, or participate in, the secondary response to glucocorticoids.