Upon the addition of small amounts of sodium dodecyl sulfate (SDS), the helicity of human serum albumin (HSA), lost in the urea denaturation, was mostly recovered. The profile of the recovery differed depending on the urea concentration. Then the urea concentrations were divided into three ranges: [1] a range below 3 M where the helicity only decreased as in the absence of urea (the helicity decreased down to 49% in the SDS solution); [2] a range between 4 and 8 M where the helicity initially increased up to 66% (this was the same as in the native state) and then sharply decreased; [3] a range above 9 M where the helicity only increased with an increase in added SDS concentration. When SDS was added prior to the urea denaturation, the same helicity was obtained at each surfactant concentration. Thus the SDS denaturation finally predominates over the urea denaturation. In the middle range, profiles of the structural change were rather complicated. The increase and decrease of helicity were accomplished below 3 mM SDS. It is worth noting that the helicity is recovered upon the addition of SDS less than 300 mu M in the second range except for 8 M urea ([HSA] = 10 mu M). The helicity-recovery profile of HSA differs from that of a homologous protein, bovine serum albumin, the helicity of which recovers to some degree, but not completely. This difference might be attributed to the fact that the C-terminal helical-rod of HSA is amphiphilic, while that of bovine serum albumin is hydrophobic as a whole.