All the acid-base reactions discussed in this section have been homogeneous. That is, they have taken place with all the species being in the same phase, mostly in solution (aqueous or otherwise) and some in the gas phase, as when discussing the Drago-Wayland relationship. However, some acid-base reactions take place when the species are in different phases, and these are known as heterogeneous acid-base reactions.

Some very important reactions of Lewis and Bronsted acids occur at surfaces. Surface acids are solids with a high surface area and Lewis acid sites, and are used as catalysts for hydration and dehydration reactions in the petrochemical industry.

Most catalysts are based on silica surfaces (eg. glass beads), though these surfaces themselves do not produce Lewis acid sites because the hydroxyl groups on the surface are so strongly bound. Bronsted acidity dominates, and whilst the acidity of silica surfaces is moderate, comparable to that of acetic acid, CH₃COOH, the acidity of aluminosilicate surfaces is very strong.

The weak surface Bronsted acidity of OH sites of silica gels is used in surface modification reactions to create thin films of organic groups:

or

The surfaces can thus be modified to have affinities for certain types of molecules, dependent on the nature of the organic groups used in the modification. This is very important in chromatography, as there are a wide range of coated beads to be used in the stationary phases.