Lysozyme molecule contains eleven carboxyl groups which can be classified by the titration behavior into four types, not titratable, with low pK-value, normal and with extraordinary high pK-value. Furthermore, X-ray crystallographic studies revealed that each carboxyl group can be characterized by the accessibility to the surrounding medium according to its position in the molecule in the crystalline state. The present experiments were carried out to clarify a correlation between a chemical reactivity and the physical state of the carboxyl groups by modifying them with condensing reagent carbodiimide and glycine derivatives. The results indicated that at low extent of the modification carboxyl groups were selectively modified, i.e., several carboxyl groups can be distinguished by their chemical reactivities.