Regional scale biotite and cordierite-bearing granites (s.l.) in the Variscan of the Central Iberian Zone (CIZ) are spatially closely associated with cordierite-rich nebulites and cordierite-bearing two-mica granites, and with cordierite-rich high grade hornfelses and cordieritites (>60% cordierite) that are relatively common in the aureoles of these granites. Building on published field evidence, petrological data are presented which, combined with new chemical and isotopic (Sr–Nd) modelling, indicate that the cordierite-bearing granites cannot be derived by simple anatexis of regional sedimentary protoliths; but the data are consistent with a process of reactive assimilation that involves the interaction of biotite granite magma with high-grade host rocks ranging from cordierite nebulites to andalusite-bearing cordieritites. The contribution of the postulated cordierite-rich contaminants to the diversity of cordierite granite compositions is modelled using the compositions of regional Lower Cambrian–Upper Neoproterozoic metasedimentary rocks that are generally chemically mature (CaO very rarely exceeds 1·4%). These rocks include specific horizons in which extreme chemical alteration is attributable to sediment reworking during eustatic falls in sea level. Such compositions may account for the presence of the high concentrations in Al that later produced cordieritites. Fractional crystallisation is also important, particularly in generating the more evolved cordierite granite and cordierite biotite muscovite granite compositions. Although assimilation in situ is normally regarded as a minor contributor volumetrically to evolving plutons, in this instance the emplacement of large volumes of granite magma into a high-T–low-P environment significantly increased the potential for reactive assimilation.