Steroid hormone receptors contain a reactive sulfhydryl group (or groups) required for hormone binding. In the present study, the effects of several sulfhydryl-blocking reagents on hormone binding to aporeceptors and hormone x receptor complexes were compared, with the use of preparations of chick oviduct progesterone receptor and intestinal vitamin D receptor. N-Ethylmaleimide inhibited hormone binding to aporeceptors, whereas prior hormone binding protected against inactivation. In contrast, the mercurial reagent mersalyl both inhibited hormone binding to aporeceptors and dissociated hormone x receptor complexes. Complete dissociation of these complexes was achieved within 20 to 30 min at 0 degrees C. This process was a pseudo-first order reaction with a t 1/2 much less than the t 1/2 for hormone dissociation for either receptor at 0 degrees C. Hormone displacement was a general property of mercurial reagents; several organic mercurials as well as HgCl2 were effective. In contrast, sulfhydryl-alkylating agents (maleimides, iodoacetamide) and the disulfide 5,5'-dithiobis(2-nitrobenzoate) were ineffective in displacing bound hormone from either progesterone or vitamin D receptors. Finally, hormone displacement by mersalyl was reversible; addition of excess thiol reagent displaced the bound mersalyl and regenerated hormone binding activity in good yield. This result suggests that mercurial reagents should prove useful in further study of steroid hormone receptors, for example in elution of receptors from steroid-affinity adsorbents.