Magnesium isotopic compositions of a profile through saprolites developed on a diabase dike from South Carolina have been measured in order to study the behavior of Mg isotopes during continental weathering. As weathering progresses, Mg isotopes are greatly fractionated and are correlated with Mg concentration, clay mineral proportions and density of the saprolites. δ26Mg values increase from −0.22 in the unweathered diabase to + 0.65 in the most weathered saprolite. These observations are consistent with the release of light Mg to the hydrosphere and formation of isotopically heavy Mg in the weathered products. The loss of Mg during weathering can be modeled by Rayleigh distillation with an apparent fractionation factor between the saprolite and fluid (α) of 1.00005 to 1.0004, i.e., up to 0.4‰ fractionation in the 26Mg/24Mg ratio between the saprolite and fluid. The large variation in α value reflects a mineralogical control on Mg isotope fractionation during primary dissolution of Mg-rich minerals and formation of secondary minerals during continental weathering. Like Mg isotopes, Li isotopes in the saprolite profile are also greatly fractionated, with δ7Li values ranging from −6.7 down to −20. The large Li isotope fractionation and variation in Li concentration, as well as irregularities in the δ7Li profile with depth, however, cannot be explained by Li loss during weathering alone. Instead, Li can be modeled by a two-step process: (1) equilibrium isotope fractionation during continental weathering, which lowered δ7Li and Li concentrations and produced a Li concentration gradient in the saprolites like that seen in Mg, and (2) subsequent kinetic isotope fractionation produced by diffusion of Li in the saprolites, possibly across a paleo-water table. The results presented here suggest that continental weathering will shift the Mg isotopic composition of the continental crust to values higher than the mantle value, whereas crustal recycling over the history of the Earth will have no discernible effect on the Mg isotopic composition of the mantle.