Mafic granulites in the Archean Quetico subprovince, north of Manitouwadge, Ontario, occur as isolated lenses or discontinuous layers in spatial association with tonalitic leucosomes in metasedimentary rocks and exhibit concentric zoning from a biotite-rich margin to an orthopyroxene-rich outer zone and a clinopyroxene-rich central zone, with internal orthopyroxene-bearing leucosomes and, rarely, patches of relict amphibolites within the clinopyroxene-rich zone. Microstructural and microchemical evidence suggests that the mafic granulites formed from amphibolites by combined infiltration-diffusion processes in the presence of a P-F-bearing silicate melt ((P2O5)melt = 0.24-0.28 wt.%) and a CO2-rich (hypersaline?) fluid. The whole-rock and mineral δ18O values of the mafic granulites (8-9 V-SMOW) indicate oxygen-isotope equilibration between amphibolites (6.6-6.9) and associated tonalitic leucosomes (9.5-10) at 700-800°C. Strontium- and Nd-isotope data and U-Pb zircon ages confirm isotopic homogenization at the leucosome-amphibolite boundaries during the peak granulite-facies metamorphism at about 2650 Ma. Texturally, early CO2-rich fluid inclusions in quartz and garnet yield P-T conditions similar to those of the peak granulite-facies metamorphism. Hypersaline fluid inclusions occur in textural coexistence with the early CO2-rich inclusions, but are invariably low in homogenization temperatures (178-234°C). This study shows that silicate melts not only provide a conduit for CO2-rich fluids but also interact directly with country rocks for the formation of granulites. Also, the O-Sr-Nd isotope data show that the documented mobility of rare-earth elements in the Quetico granulite zone is localized in scale and related to anatexis of local metasedimentary rocks during the granulite-facies metamorphism.