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Nd, Sr and O isotopic data were obtained from silicic ash-flow tuffs and lavas at the Tertiary age (16-9 Ma) Timber (Mountain/Oasis Valley volcanic center (TMOV) in southern Nevada, to assess models for the origin and evolution of the large-volume silicic magma bodies generated in this region. The large-volume (> 900 km3), chemically-zoned, Topopah Spring (TS) and Tiva Canyon (TC) members of the Paintbrush Tuff, and the Rainier Mesa (RM) and Ammonia Tanks (AT) members of the younger Timber Mountain Tuff all have internal Nd and Sr isotopic zonations. In each tuff, high-silica rhyolites have lower initial epsilon-Nd values (approximately 1 epsilon-Nd unit), higher Sr-87/Sr-86, and lower Nd and Sr contents, than coerupted trachytes. The TS, TC, and RM members have similar epsilon-Nd values for high-silica rhyolites (-11.7 to -11.2) and trachytes (-10.5 to -10.7), but the younger AT member has a higher epsilon-Nd for both compositional types (-10.3 and -9.4). Oxygen isotope data confirm that the TC and AT members were derived from low delta-O-18 magmas. The internal Sr and Nd isotopic variations in each tuff are interpreted to be the result of the incorporation of 20-40% (by mass) wall-rock into magmas that were injected into the upper crust. The low delta-O-18 magmas most likely formed via the incorporation of low delta-O-18, hydrothermally-altered, wall-rock. Small-volume rhyolite lavas and ash-flow tuffs have similar isotopic characteristics to the large-volume ash-flow tuffs, but lavas erupted from extracaldera vents may have interacted with higher delta-O-18 crustal rocks peripheral to the main magma chamber(s). Andesitic lavas from the 13-14 Ma Wahmonie/Salyer volcanic center southeast of the TMOV have low epsilon-Nd (-13.2 to -13.8) and are considered on the basis of textural evidence to be mixtures of basaltic composition magmas and large proportions (70-80%) of anatectic crustal melts. A similar process may have occurred early in the magmatic history of the TMOV. The large-volume rhyolites may represent a mature stage of magmatism after repeated injection of basaltic magmas, crustal melting, and volcanism cleared sufficient space in the upper crust for large magma bodies to accumulate and differentiate. The TMOV rhyolites and 0-10 Ma old basalts that erupted in southern Nevada all have similar Nd and Sr isotopic compositions, which suggests that silicic and mafic magmatism at the TMOV were genetically related. The distinctive isotopic compositions of the AT member may reflect temporal changes in the isotopic compositions of basaltic magmas entering the upper crust, possibly as a result of increasing ’’basification’’ of a lower crustal magma source by repeated injection of mantle-derived mafic magmas.