Molecular dynamics (MD) techniques have been employed to address the structural evolution of highly charged disulfide-bond-reduced lysozyme (DR-LYZ) in vacuo, starting from a compact, nativelike conformation. The results obtained are discussed in terms of factors that promote the stability of lysozyme and are contrasted with the structural evolution of disulfide-bond-intact lysozyme (DI-LYZ), simulated under the same conditions (Reimann et al., Phys. Rev. E, 1999, 60, 7277-7284). For DR-LYS, at least three types of unfolded structures were observed: A, expanded but near-native conformations; B, conformations with the C-terminus portion of the traditionally denoted alpha domain (alpha(2)) extended; and C, conformations that: were overall extended. Generally, higher charge states led to enhanced unfolding, but the charge-state threshold for achieving a certain degree of unfolding depended on temperature and charging configuration. Similar patterns of charge self-solvation were observed in many of the unfolded structures. The beta domain, along with the N-terminus portion of the alpha domain (alpha(1)), emerge as robust structural features which were stabilized both by their own internal hydrogen and self-solvation bonds, as well as by their interactions with each other and with portions of alpha(2).