The Cascade arc is the warm-slab subduction zone global end member, where a broad variety of primitive magmas with highly variable slab fluid signatures have erupted in close spatial and temporal proximity. A number of petrogenetic models have been proposed to explain the occurrence of such diverse magmas, but the source (s) of these magmas and the timing of fluid addition to the sub-arc mantle remain controversial. We present uranium-series isotope data (U-238-Th-230-Ra-226) for eighteen mafic lavas from the Three Sisters region of the central Oregon Cascades, and for a further six lavas from the rear-arc Newberry Volcano. The majority of these samples have geochemical characteristics (e.g. Nb/Zr, Ba/Zr, Sr-87/Sr-86) consistent with previously described calc-alkaline basalts from this region of the arc, and indicative of limited fluid involvement at some stage in their genesis. Trace element and long-lived radiogenic isotope modeling suggests that this fluid was derived from dehydration of subducting sediments, and was added to an enriched, garnet-bearing mantle wedge source. The trace element systematics of the lavas are consistent with small degree (<10%) melts of this fluid-modified source. All samples display (Th-230/U-238) and (Ra-226/Th-230)>= 1, similar to values measured in fresh MORB and other parts of the arc. Results of a dynamic melting model support the interpretation that these lavas are small degree melts of an asthenospheric source, and do not allow for a lithospheric mantle source. However, the U-series data do not permit us to determine whether fluid addition was the trigger for melting, or whether the lavas were generated from a secular equilibrium source that had experienced fluid addition >350 ka prior to melting. Regardless, modern fluid input is limited and melting is dominantly occurring in response to upwelling and decompression. (C) 2011 Elsevier B.V. All rights reserved.