TMAO is a naturally occurring protecting osmolyte which stabilizes proteins and influences intermolecular interactions. Like some other osmolytes it counteracts the effects of urea in an additive manner. Thermodynamic analysis reveals that the association constants of urea or protecting osmolytes are close to 1M-1 implying that even at high concentrations only a small fraction of possible binding sites is occupied. There would therefore be no competition between osmolytes which could thus act independently. However, we have shown that TMAO and urea do not act independently but form a strong complex in solution. These results have also resolved many of the contradictions in the literature and shown that the effect of TMAO on proteins in solution must be indirect. The aim of the proposed experiments is to verify the stoechiometry of the TMAO:urea complex in solution.