Several different solvent systems are commonly used to dissolve Bombyx mori silk fibroin to prepare regenerated silk membranes and fibers though differences in the behavior of these solvents have not been fully investigated. Here we compare the effects of four of these on the rheology of silk fibroin solutions and on protein secondary structure as revealed by FTIR spectroscopy of cast membranes. The results demonstrated that Ca(NO3)(2)-MeOH-H2O and LiBr-EtOH-H2O had the strongest solvation on the silk fibroin chains, which showed an almost constant viscosity (Newtonian behavior) over most of the shear rate range (0.1-500 s(-1)). In contrast, the 9.5 M aqueous LiBr appeared to have the weakest solvation with similar effects on the silk fibroin molecules to pure water as indicated by rheological behavior. It was also found that the silk fibroin membranes prepared using all four solvent system showed mainly random coil conformation with a small proportion of P-sheet by FTIR spectroscopy. We discuss the implications of these findings for the preparation of regenerated silk for different applications.