It is shown that the exchange-dispersion energy contribution of symmetry-adapted intermolecular perturbation theory (SAPT) can be evaluated without invoking the single-exchange approximation in the case of single-determinant ground-state references. A succinct expression is derived which allows for efficient implementation. Making use of the corresponding exchange-induction contribution, obtained recently, this enables DFT-SAPT calculations, i.e., SAPT based on a density-functional theory description of the monomers, without an expansion in orders of the intermonomer overlap S. The approach is used to test the quality of the S 2 or single-exchange approximation for the systems He2, Ar2, N2–Ne, H2O–Ar, (H2O)2 and LiF, i.e., van der Waals and hydrogen-bridged complexes as well as an ionic molecule. While employing the S 2 approximation for the exchange-dispersion contribution is found to have minor impact on total SAPT interaction energies, its use to evaluate the exchange-induction contribution significantly affects the quality of the repulsive branches of the potential energy curves for the interacting partners. Adding appropriate Hartree–Fock level estimates of higher-order induction plus exchange-induction energies, however, restores good agreement with complete basis set limit coupled-cluster results.