1-Methoxynaphthalene (1) undergoes regioselective lithiation in position 2 (n-BuLi/TMEDA) or in position 8 (t-BuLi), respectively. The detected formation of a n-BuLi/1 complex (1:1 n-BuLi/1 mixture) appears to have only minor influence on the regioselectivity (both products are obtained). The exchange of hydrogen atom H2 by deuterium results in a remarkably reduced reaction rate for the lithiation with n-BuLi in THF-d(8). This isotope effect and the formation of the thermodynamically less favorable 2-lithio compound suggest a kinetically controlled mechanism. The lack of an isotope effect for the reaction of 8-deuterio-1-methoxynaphthalene with t-BuLi and the formation of the thermodynamically preferred 8-lithiated product indicate a thermodynamically controlled mechanism. Slow conversion of the 2- into the 8-lithiated species (at higher temperatures) gives further evidence that n-BuLi and t-BuLi afford the kinetically and thermodynamically preferred products, respectively.