The assumption that the isotopic ratios of anatectic melts generated in response to crust-magma interaction are equivalent to the bulk source rock from which they are derived was tested experimentally via dehydration melting of a Proterozoic biotite granite. Heating of the coarse-grained granite at 1250 °C for durations of 1 to 48 h produced extreme disequilibrium among simultaneously generated mafic and felsic melts (quenched to glass) and whole-rock 87Sr/86Sr ratios. In-situ microdrill Sr isotopic analyses across gradational contacts between mafic (high-87Sr/86Sr) and felsic (low-87Sr/86Sr) glass register significant isotopic and chemical heterogeneity on the submillimetre scale. Our experiments suggest that during the early stages of wall-rock melting, when the rate of heating may exceed melting rates, isotopic equilibrium may not be maintained, thus producing contaminant liquids having isotopic compositions different from the bulk source rock. If isotopic equilibrium is not attained during partial melting in the crust, current geochemical models of open-system magmatic processes may require modification.