The acid induced ring opening of (R)-(+) styrene oxide (1R) or (S)-(−) styrene oxide (1S) is investigated in the gas phase, at a temperature of 25 °C and in the presence of a labeled nucleophile (CH318OH, CD3OH, or H218O). Various acid catalysts are generated in situ by γ radiolysis of the bulk gas (720 Torr of CH4 or CH3F). The mechanisms of the ring-opening reaction are assessed by modulating the composition of the gaseous mixture. Two reaction pathways are operative in the gas phase, both proceeding with the same regio- (100% at Cα) and stereochemistry (55–67% inversion of the Cα configuration). In the CH3F/H218O systems, a slow reaction takes place within a persistent proton-bound complex between the epoxide and the CH318OH2+ ion, formed by (CH3)2F+-methylation of H218O (the intracomplex pathway). When methanol is present in the gaseous mixtures, the intracomplex process is superseded by a faster extracomplex reaction, involving the attack of an external methanol molecule on the O-protonated epoxide. The present results are discussed in the light of related gas-phase and solution data.