The divalent binding of a bis(adamantyl)-functionalized calix[4]arene (1) to an EDTA-tethered beta-cyclodextrin (CD) dimer (2) in solution (1.2 x 10(7) M-1) was 3 orders of magnitude weaker than the binding constant (similar to10(10) M-1) for the interaction of 1 at CD self-assembled monolayers (SAMS) on gold. This difference in binding is rationalized using a theoretical model, which interprets the divalent binding as two consecutive monovalent binding events, i.e., an intermolecular interaction followed by an intramolecular binding event, the latter of which is associated with an effective concentration term accounting for the close proximity of the two interacting species. The methodology presented in the model is applicable to divalent binding both in solution and at SAMS and indicates that the difference in observed binding constants mainly stems from a difference in effective concentration.