Rates of acid-catalyzed methoxy exchange between methanol and the three diastereomers of 2-methoxy-4,6-dimethyl-1,3-dioxane (6) were measured in benzene, and the rates for the two cis diastereomers were measured in methanol/chloroform. Rate constants were evaluated using a 1D-EXSY NMR pulse sequence and a weighted linear least squares analysis. Rates of methanol attack on the cationic intermediate (8) show 24-fold axial selectivity in benzene and 9-fold selectivity in methanol/chloroform. A ring-opening mechanism for equatorial exchange can be rejected, since rate constants k(ea) and k(ae) for direct axial/equatorial epimerization are zero. These results demonstrate that antiperiplanar lone pairs are more effective in this system than syn, although the effect is worth no more than 2 kcal/mol.