Nd, Sr, and Pb isotope ratios have been determined for 60 samples (lavas, tuffs, pumices, and feldspar separates) of 27 volcanic units (lavas and ash flow tuffs) from the Indian Peak and Central Nevada caldera complexes from the southern Great Basin of Utah and Nevada. O-isotope data for these units were acquired by Hart (1997) and Larson and Taylor (1986). Volcanic rocks for the two subduction-related caldera complexes have similar ages (Eocene to Oligocene) and range from andesite to rhyolite of the high-K, calcalkaline series. Whereas they have overlapping initial Sr-isotope ratios (0.706 to 0.712), they have strikingly different Pb, Nd, and O isotopic compositions. Rocks from Indian Peak caldera complex have lower 206Pb/204Pb (18-18.5) and 207Pb/204Pb (15.55-15.65) than those from the Central Nevada caldera complex (19-19.6 and 15.7-15.8), but both have comparable 208Pb/204Pb ratios (38.8-39.7). The epsilon Nd values of dacites and rhyolites from the Central Nevada caldera complex (-6 to -11) are systematically higher than those of the Indian Peak complex (-12 to -18). Delta 18O values in quartz are also higher in the volcanic rocks of the Central Nevada complex than those from Indian Peak (10.5 versus 9.5 per mil). Moreover, andesites from the Central Nevada caldera complex region are depleted in Al, Na, and U and enriched in Ca, Mg, Cr, Y, and Nb compared to other andesites from the Great Basin. We suggest that mantle-derived magmas of the Central Nevada caldera complex interacted extensively with a thick upper crustal section of Proterozoic and Paleozoic carbonates and quartzites (high Ca, Mg; low Na, Al, and U; high 18O, 206Pb/204Pb) perhaps doubled by Sevier-age thrusting. On the other hand, Indian Peak caldera complex magmas had crustal components dominantly from a metamorphic basement of Proterozoic age (modest 18O, low epsilon Nd, and low 206Pb/204Pb). These isotopic and compositional differences are consistent with the presence of a fundamental NE-trending crustal boundary between the two complexes that probably corresponds to the boundary between the central Great Basin (Central Nevada caldera complex) and Mojave (Indian Peak caldera complex) Pb-isotope provinces of Wooden et al. (1998).