We have constructed novel chimeric receptors consisting of the activation region of the herpes simplex virus transcription factor VP16 inserted into the amino-terminal region of the human estrogen receptor containing or lacking the hormone-binding region. By gene transfer into mammalian cells, these chimeric receptors behave in a hormone-dependent or hormone-independent manner, respectively, and are more efficient activators of gene expression than wild-type estrogen receptor. These studies indicate that a potent activation region from a viral transcription factor can be placed under hormonal control when introduced into a steroid receptor molecule and can enhance the receptor's potency (approximately 10-fold) in activating specific gene expression. It is likely that such chimeric molecules could be designed to increase selected target gene responses to any intracellular receptor in the course of cellular transfection, transformation, or transgenic animal experiments.