Oxygen-isotope analyses of a 37-km2 exposure of Precambrian granite adjacent to the Miocene Lake City caldera are used to document interactions with a 23-m.y.-old meteoric-hydrothermal system established within the caldera. The granite δ18O values range from +0.7 to +9.2, all lower than for the original granite (∼ +9.5), indicating pervasive exchange with a low-18O fluid. Primary muscovite exchanged oxygen with the fluid faster than did quartz, but much more slowly than did K-feldspar, and primary biotites were altered to variable mixtures of low-18O chlorite and sericite. The granite was altered over a wide range of water/rock ratios in two distinct regimes, a sericite alteration regime and a chlorite alteration regime. Granite in the highly faulted Eureka graben exhibits the lowest whole-rock δ8O values and the highest degree of biotite alteration; this zone was a main channel for fluid flow through the granite. Groups of samples (3) are defined relative to the graben axis: (1) a “graben group” with whole-rock δ18O=0 to +4; (2) an intermediate group (5.5 to 9.0 km from the graben axis) with δ18O=+2 to +8 that shows a positive correlation between sample elevation and whole-rock δ18O; (3) a distal group (>9.0 km) with δ18O=+6 to +9 that also shows a positive correlation between elevation and δ18O. These δ18O-elevation trends (∼0.7 per mil/100 m) imply a systematic vertical thermal gradient in the near-surface portions of the granite during hydrothermal activity, as well as a lateral gradient in water/rock ratio outward from the graben. A subgroup of samples within the intermediate group is from a postcaldera structural dome, and the δ18O-elevation trends in the granite are offset by the uplift.