We report here a synthetic study on the formation process of hollow polymeric nanospheres based on a simple, core-template-free route, and the effects of polymerization concentration, shell cross-linking, pH, salt concentration and temperature on the size and stability of hollow polymeric nanospheres. The hollow structure of polymeric nanospheres is spontaneously formed by polymerization of acrylic acid monomers inside the chitosan-acrylic acid assemblies. It is found that (i) the hollow structure of nanospheres is stabilized by both physical cross-linking in the inner shell and chemical cross-linking in the outmost shell; (ii) the size of the hollow spheres can be adjusted over the range of 77-500 nm by controlling the concentration of chitosan-acrylic acid assemblies in the reaction system; (iii) the synthesized nanospheres are stimuli-responsive. The size of the hollow nanospheres can be manipulated by changing pH, salt concentration and temperature. Furthermore, with heating and cooling the variation in size of hollow nanospheres is completely reversible and reproducible; (iv) the surface of the hollow nanospheres obtained is chemically active, which provides the functional sites with chemical groups for subsequent chemical reactions at the surface. (c) 2005 Elsevier Ltd. All rights reserved.