A remarkably high viscosity has been induced in protein aqueous solutions by the addition of certain structurally related organic solvents, The effect has been observed for lysozyme aqueous solutions containing tetramethylurea (TMU), dimethylsulfoxide (DMSO), dimethylformamide, and hexamethylphosphortriamide. The effect has also been induced in ferrocytochrome c aqueous solutions by TMU, Critical concentrations for both the protein and organic solvent were verified for the onset of the viscosity increase, A common feature of the solvents which were able to induce the effect is a dipolar moiety (C = O, S --> O and P --> O) and a nonpolar region represented by the methyl groups. The resulting fluids show an extremely restricted flow and a typical non-Newtonian, pseudoplastic behavior, Use was made of H-1 nuclear magnetic resonance (NMR) and Raman spectroscopy to characterize protein structural modifications and of C-13 NMR to investigate changes in relaxation times and chemical shifts in the solvent/water solutions. A systematic rheological characterization of the systems was undertaken for some of the solvents, and unusual patterns of viscous effects were identified for the solvent/water systems both with and without protein, The process was found to be at least partially reversible, as concluded from the recovered original solution rheological characteristics and the original protein H-1 NMR spectrum, after eliminating the organic solvent by ultrafiltration. The whole process was characterized as consisting of two mutually independent stages, The first involves an extensive conformational transition of the polypeptide backbone, from a predominantly alpha-helical to increased random coiled and beta-sheet structures, with the occurrence of nonorthodox protein secondary structures at regions above the solvent critical point, The second stage consists of short-lived interchain contacts leading to an entanglement of the macromolecular system as a whole. A microphase reversion in the organic solvent/water mixture, supported by C-13 NMR and rheological results, is proposed as the driving force causing the observed behavior.