Differential scanning calorimetry (DSC) was used, in conjunction with two functional assays that monitor binding, in a storage stability study on a protein of pharmaceutical interest, the soluble form of the T-lymphocyte multidomain surface receptor, sCD4. DSC monitored structural changes in binding and non-binding domains. ELISA, using the monoclonal antibody OKT4a, and frontal elution affinity chromatography, using the HIV surface glycoprotein, gp120, monitored function of the binding domain. The stability of sCD4 in a solution formulation was followed for up to 30 days at five different pHs ranging from 5.0 to 7.9 and five different temperatures ranging from -70°C to 40°C. While the overall trends observed with the three techniques were the same, the ELISA data were somewhat less reproducible than those for the other methods. Furthermore, the results suggest that DSC is more sensitive to structural changes that would reduce the protein's bioactivity. The results of this study indicate DSC's utility, in conjunction with quantitative functional analysis, in the formulation of protein-containing pharmaceuticals or foods, especially those containing multiple-domain proteins. © 1996 Akadémiai Kiadó.