The interaction between lysozyme and oppositely charged poly(acrylic acid) microgels was investigated by micromanipulator-assisted light microscopy, confocal microscopy and circular dichroism. Lysozyme uptake and distribution within the microgel particles, and its effect on microgel deswelling, was studied regarding effects of pH, ionic strength and lysozyme concentration. For a range of conditions, lysozyme distributes nonuniformly within the microgels, forming a lysozyme/microgel shell in the outer parts of the microgel. This shell formation is associated both with increased lysozyme loading to the microgels and with increased lysozyme-induced microgel deswelling. At high microgel charge density, the shell formation displays nonmonotonic ionic strength dependence. The shells formed are characterized by a net positive charge, and by relatively fast exchange of lysozyme between shell and solution, although the exchange kinetics decreases strongly with decreasing ionic strength. At conditions of slower exchange kinetics, the shells are characterized by an effective pore size of less than about 4 nm. (C) 2007 Elsevier Inc. All rights reserved.