The influence of tectonic setting and age on the variation of isotopic signatures of granitic plutons in the northern Great Basin has, in general, not been apparent from previous investigations. Although Elison et al. pointed out isotopic differences between Jurassic and younger plutons near the 0.706 Sr isopleth, and Farmer and DePaolo noted that there might be a difference between Cenozoic vs. Mesozoic plutonic rocks in the eastern part of the northern Great Basin, neither of these studies revealed the remarkable correlation between isotopic signature, age, and tectonic setting shown by our expanded Sr, Nd, and Pb isotopic data base. Jurassic-Early Cretaceous plutons in the northern Great Basin have a limited range of Sr and Nd isotopic values that cluster near bulk earth. All but one of these plutons have ϵNd values less negative than -7 despite their location both to the west and east of the ϵNd = -7 line. Construction of Sr 0.706 and ϵNd = -7 isotopic boundaries is virtually impossible for plutons of this age range. In contrast, Upper Cretaceous peraluminous granites east of the ϵNd = -7 line have very negative ϵNd values and high initial Sr ratios, and they appear to represent essentially pure crustal melts. The data favor a model that equates generation of these plutons via crustal thickening associated with the Sevier thrust belt. Cenozoic plutons appear to be mixtures of mantle and crustal reservoirs, and their isotopic systematics, along with those of the Late Cretaceous age plutonic suite, define a previously unrecognized, approximately east-west-trending crustal boundary between predominantly Archean crust to the north and predominantly Proterozoic crust to the south. The isotopic data from the Jurassic-Early Cretaceous plutonic suite do not reflect the presence of this boundary, suggesting that the isotopic systematics of this plutonic suite may not have been controlled by the same variations in crustal and/or mantle lithospheric structure at depth.