The interaction of cutinase from Humicula insolens (HiC) and sodium dodecyl sulfate (SDS) has been investigated by small-angle neutron scattering (SANS) and isothermal titration calorimetry (ITC). The concerted interpretation of structural and thermodynamic information for identical systems proved valuable in attempts to elucidate the complex modes of protein-detergent interaction. Particularly so at the experimental temperature 22 degrees C, where the formation of SDS micelles is athermal (deltaH = 0), and the effects of protein-detergent interactions stand out clearly in the thermograms. It was found that the effect of SDS on cutinase depended strongly on the sample composition. Thus, addition of SDS corresponding to a molar ratio, n(s) = n(SDS)/n(HiC) of about 10, was associated with the formation of HiC/SDS aggregates, which include more than one protein molecule. The SANS results suggested that on the average such adducts contained two HiC, and the ITC traces showed that they form and break down slowly. At slightly higher SDS concentrations (n(s) = 10-25) these "dimers" dissociated, and the protein denatured. The denaturation showed the characteristic positive enthalpy change, but the SDS denatured state of HiC was unusually compact with a radius of gyration close to that of the native conformation. Further titration with SDS was associated with exothermic binding to the denatured protein until the saturation point at about n(s) = 90. At this point, the free monomer concentration was 2.2 mM and the binding number was approximately 40 SDS/HiC. Interestingly, this degree of SDS binding (approximately 0.5 g of SDS/g of HiC) is less than half the amount bound to typical water-soluble proteins.