The contribution of plasma membrane-associated glucocorticoid receptor (GR) to transcriptional signaling is unclear. We observed GR in-low-density detergent-resistant membrane (DRM) rafts derived from human hepatoma Hep3B cells in complexes with caveolin-1, HSP90, and STAT3. In transient transfection assays, GR-stimulated transcriptional signaling was reversibly inhibited by membrane-raft disrupters filipin III and progesterone. These data provide clear evidence for a functional contribution of DRM-associated GR to transcriptional signaling. (c) 2005 Elsevier Inc. All rights reserved.