This Letter reports a FTIR study on the pressure-induced unfolding of lysozyme in pure D2O close to the conditions of non excess hydration. An essential population of the proteins apparently refold into its native structure after pressure release. It could furthermore be shown that down to a hydration of h = 2 ( h = m(prot)/m(D2O); m = mass), the unfolding pressure did not vary with hydration. Hydration dependent behaviour was found with respect to the change of the wavenumbers of the alpha-helical structure during unfolding. This result is discussed with respect to the reversibility of unfolding in pure solvents and with the effects of hydrogen exchange. (C) 2008 Elsevier B. V. All rights reserved.