THE Saccharomyces cerevisiae SNF2/SWI2 protein is essential for the regulated expression of a variety of genes(1,2). A human SW12/SNF2 homologue, hBrm, is a positive participant in glucocorticoid-receptor-mediated transcription(3), but its mechanism of action is not known. The retinoblastoma protein, RB, has also been shown to stimulate the transcription of several genes(4-10), although the target for RB has not been identified in any of these transcriptional events. Here we show that RB upregulates glucocorticoid-receptor-mediated transcription. The effect of either RB or hBrm is dependent on the presence of the other. Furthermore, we demonstrate that RB and hBrm interact with one another in vitro and in vivo. These results highlight a new role for RB, which is to interact with hBrm in order to potentiate glucocorticoid-receptor-activated transcription.