We present a hybrid quantum mechanical/molecular mechanical (QM/MM) molecular dynamics study of dimethyl ether (DME) and 18-crown-6 (18c6) interacting with K+. The QM/MM method employs the semiempirical AM1 method to describe the ethers, the MM parametrization of Dang for K+, and the MM SPC/e model for H2O. We parametrize the interaction Hamiltonian to the binding energies and optimized geometries for K+/DME using ab initio HF and MP2/6-31+G* results. The resulting QM/MM model describes the polarization response of both free DME and K+-complexed DME well. The QM/MM model gives good agreement with the experimental and ab initio structures for K+/18c6. We calculate gas-phase K+/18c6 binding energies of -70.2 and -72.0 kcal/mol with the QM/MM and MP2/6-31+G* (CP corrected) methods, respectively. Our simulation results for K+/18c6 in H2O show that the most probable K+/18c6 center-of-mass displacement is 0.25 Angstrom, in marked contrast to previous molecular dynamics results of Dang and Kollman. Our result is consistent with K+ having an optimal "fit" for the cavity of 18c6. Still, we find that K+ retains significant solvent accessibility coordinating two H2O molecules, on average, in the K+/18c6 simulation. The simulation average polarization energy for 18c6 interacting with both K+ and the H2O solvent is -14.9 kcal/mol, which is 17% of the total electrostatic interaction energy. This result underscores the potential importance of QM in describing the solution chemistry of ion-macrocycle interactions. Our study is the first simulation of crown ethers that explicitly incorporates QM in the force field.