Stimuli-responsive organic-inorganic hybrid spheres were synthesized by coating the colloidal polystyrene spheres with polyelectrolyte-protected aminoclay, Mg phyllo(organo)silicate layers in a layer-by-layer method. The clay layers are sandwiched between the polyelectrolyte layers. The aminoclay swells in water due to protonation of amino groups, and the degree of swelling depends on the pH of the medium. As a result, the hybrid spheres undergo a size change up to 60% as the pH is changed from 9 to 4. The stimuli-responsive property of the hybrid spheres was used for the release of ibuprofen and eosin at different pH. © 2010 American Chemical Society.