Structural rearrangements and aggregation resulting from covalent modification of human IgG by caprylic ester of N-hydroxysuccinimide were studied by differential scanning calorimetry, dynamic light scattering, and ANS-binding spectrofluorimetry. The thermogram for the native IgG displays only one transition peak (Tmax = 68°C, ΔH = 20.9 ± 0.3 J/g). For the chemically modified IgG the temperatures corresponding to the initial and maximal deviations of the heat flow as well as the area under the transition peak decreased as the number of attached alkyl groups increases. This finding may be explained by weakening the intramolecular interactions responsible for the rigidity of the IgG molecular structure and by an increase in the protein-protein interactions for the modified IgG. Dynamic light scattering data indicate spontaneous aggregation of the modified IgG molecules in aqueous solution; the size of aggregates depends on the modification degree. These data correlate with a drastic increase in the surface hydrophobicity index for IgG molecules with an increase in the number of attached alkyl chains.