Experimental and theoretical studies of the regioselective deprotonation of thiirane S-oxides are reported. Experimentally under the reaction conditions of LiHMDS/THF/-78 degrees C with anti-alkylthiirane S-oxides or anti-silylthiirane S-oxides as starting materials, the products of ring-opening are (E)-2-alkylethenesulfenate and 1-silylethenesulfenate anions, respectively. Experiments involving deuterium labeling clearly indicate that a regioselective deprotonation reaction was followed by a stereoselective ring-opening. Ab initio methods at both the Hartree-Fock and Moller-Plesset perturbation theory levels with the 6-31+G(d) basis set were used to examine both lithiated methyl- and silylthiirane S-oxides. Of the possible anti-substituted species, the coordination of the lithium anti to the methyl and gem to the silyl is predicted to be the most stable. These stable intermediates with the lithium syn to the sulfoxide could ring-open to yield the experimentally observed products.