We report that the presence of very low concentrations (<0.1 M) of urea, a widely used chemical denaturant, induces structure formation in the water-sobluble globular protein human serum albumin (HSA) at pH 7. We have presented results suggesting an almost 8% and 5% increase in α-helix in the presence of 10 mM urea (U) and 20 mM monomethylurea (MMU), respectively. Far and near-UV circular dichroism studies along with tryptophan fluorescence and 1-anilino-8-naphthalenesulphonicacid (ANS) binding support our view. We hypothesize that both U and MMU, at such low concentrations, modify the solvent structure, increase the dielectric constant and consequently increase hydrophobic forces resulting in enhanced α-helical content. The implications of these results of the lower urea regime are significant because the physiological blood urea ranges from 2.5 to 7.5 mM. © 2006 The Japanese Biochemical Society.