At first glance, signaling by steroid hormone receptors seems simple-these receptors are intracellular proteins that, upon activation by hormone, act as regulators of transcription. Thus, we can imagine a minimalist scheme: Hormone binds to the receptor, inducing a conformational change such that the receptor now binds DNA and modulates transcription. Alas, this fanciful view is far from accurate. There are numer-ous otherkey participants in steroid signaling, notably the molecular chaperones (1), proteins that assist protein folding in general. Two recent reports (2, 3), one in this issue of Science (2), identify DnaJ, an old friend in chaperone circles, as a new player in steroid receptor function; the findings suggest multiple roles for DnaJ in steroid signaling. Their wider implication is that a subset of molecular chaperones may be uni-versally required for signal transduction. In the absence of hormone, certain ste-roid receptors, including the glucocorticoid, androgen, andestrogen receptors, are found as" aporeceptor complexes" consisting of a receptor monomer, a dimer of the heat shock protein Hsp90, and several other proteins (1, 4)(see figure). Subsequent to ligand binding, the" activated receptor" dis-sociates from the complex, binds to specific DNA sequences, and modulates the tran-scription of genes. Proper interaction of the receptors with Hsp90 is essential for effi-cient ligand binding and response (5-7), in-dicating that theaporeceptor complex rep-resents a" poised" conformation of the re-ceptor, ready to respond to signal. In the ab-sence ofligand, the complex is in dynamic equilibrium with two unliganded, non-Hsp90-bound receptor forms (steps A and B in the figure). Hsp70and other chaper-ones, in an adenosine triphosphate (ATP)-dependent mechanism, appear to reas-semble Hsp90 onto the unliganded receptors, thereby maintaining the pool of aporeceptors that can respond to ligand (6). Interestingly, steroid receptor mutants lack-ing the" signaling domain," the region of the receptor that interacts with ligand and