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Mafic enclaves are commonly found in intermediate arc magmas, and their occurrence has been linked to eruption triggering by pre-eruptive magma mixing processes. New major, trace, Sr Nd and U Th isotope data of rocks from Nisyros in the Aegean volcanic arc are presented here. Pre-caldera samples display major and trace element trends that are consistent with fractionation of magnetite and apatite within intermediate compositions, and zircon within felsic compositions, and preclude extensive hybridization between mafic and felsic magmas. In contrast, post-caldera dacites form a mixing trend towards their mafic enclaves. In terms of U-series isotopes, most samples show small 238U excesses of up to ˜ 10%. Mafic enclaves have significantly higher U/Th ratios than their dacitic host lavas, precluding simple models that relate the mafic and felsic magmas by fractionation or aging alone. A more complicated petrogenetic scenario is required. The post-caldera dacites are interpreted to represent material remobilized from a young igneous protolith following influx of fresh mafic magma, consistent with the U Th data and with Sr Nd isotope constraints that point to very limited (< 10%) assimilation of old crust at Nisyros. When these results are compared to data from Santorini in the same arc, there are many geochemical similarities between the two volcanic centers during the petrogenesis of the pre-caldera samples. However, striking differences are apparent for the post-caldera lavas: in Nisyros, dacites show geochemical and textural evidence for magma mixing and remobilization by influx of mafic melts, and they erupt as viscous lava domes; in Santorini, evidence for geochemical hybridization of dacites and mafic enclaves is weak, dacite petrogenesis does not involve protolith remobilization, and lavas erupt as less viscous flows. Despite these differences, it appears that mafic enclaves in intermediate Aegean arc magmas consistently yield timescales of at least 100 kyrs between U enrichment of the mantle wedge and eruption, on the upper end of those estimated for the eruptive products of mafic arc volcanoes. Finally, the data presented here provide constraints on the rates of differentiation from primitive arc basalts to dacites (less than ˜ 140 kyrs), and on the crustal residence time of evolved igneous protoliths prior to their remobilization by mafic arc magmas (greater than ˜ 350 kyrs).