The three main types of hydroxyl groups on a silica surface are classified as isolated, hydrogen bonded, and inaccessible. The isolated and hydrogen bonded groups are the most important as these readily exchange with D2O and thus are exposed to reactant molecules. However, it has generally been accepted that the inaccessible groups do not participate in surface reactions as only a small fraction of these groups exchange with D2O. It is shown that the inaccessible hydroxyl groups on nonporous fumed silica and mesoporous MCM-48 silica powders and films fully exchange with D2O and are reactive with octadecylydimethylchlorosilane when supercritical CO2 is used as the solvent. Furthermore, it is found that the CO2 penetrating the regions containing the inaccessible groups is not removed by simple evacuation but rather slowly diffuses from the silica over periods of months.