Stereoregular poly(methyl methacrylates) (PMMAs) solvent-cast in the form of films against a glass substrate were employed as model systems for a systematic study of the relationship between the molecular structure las characterized by the stereochemistry and conformations of macromolecules), the functional-group composition, and the wettability of polymer surfaces. The water wettability of a syndiotactic surface was found to be highly sensitive to the polarity of the adjacent phase in the film-casting process, whereas the wettability of an isotactic surface was invariant to the polarity of the contacting medium. The tacticity-dependent wetting behavior arises from the difference in the extent of functional-group surface segregation or, in other words, from the different surface activity of the different tactic versions of the polymer. This difference, in turn, is associated with fundamental distinctions in the conformational structures energetically allowed for the isotactic and syndiotactic configurations of the polymer chain; the syndiotactic macromolecule is capable of adopting an amphiphilic surface conformation, whereas the energetically allowed conformational structures of the isotactic macromolecule do not possess amphiphilic character. In view of these findings, the isotactic surfaces: can be regarded as ＇ideal＇ model surfaces for research on the fundamentals of wetting phenomena. In addition, there is evidence for failure of the basic assumption of the Cassie approach, i.e. the assumption of macroscopic chemical heterogeneity, to describe adequately the wetting behavior of isotactic PMMA surfaces.