This study reports on a model for denaturation of myoglobin by urea for concentrations ranging from 0.1 M to 15 M. The experimental data from quartz crystal microbalance (QCM), circular dichroism (CD) and dilational rheology are examined with respect to a 'structure-breaking effect' of urea on the aqueous phase. Even at urea concentrations > 10 M, native conformation of the protein is retained through a restabilization of the hydrophobic association. Our study shows that any proposed denaturation mechanism of large biomolecules requires very high concentrations of urea and the association of urea with protein water system is based on enhancement of hydrophobic interactions. (c) 2008 Elsevier B.V. All rights reserved.