Twenty vapour-phase garnets were studied in two samples of the Topopah Spring Tuff of the Paintbrush Group from Yucca Mountain, in southern Nevada. The Miocene-age Topopah Spring Tuff is a 350 m thick, devitrified, moderately to densely welded ash-flow tuff that is zoned compositionally from high-silica rhyolite to latite. During cooling of the tuff, escaping vapour produced lithophysae (former gas cavities) lined with an assemblage of tridymite (commonly inverted to cristobalite or quartz), sanidine and locally, hematite and/or garnet. Vapour-phase topaz and economic deposits associated commonly with topaz-bearing rhyolites (characteristically enriched in F) were not found in the Topopah Spring Tuff at Yucca Mountain. Based on their occurrence only in lithophysae, the garnets are not primary igneous phenocrysts, but rather crystals that grew from a F-poor magma-derived vapour trapped during and after emplacement of the tuff. The garnets are euhedral, vitreous, reddish brown, trapezohedral, as large as 2 mm in diameter and fractured. The garnets also contain inclusions of tridymite. Electron microprobe analyses of the garnets reveal that they are almandine-spessartine (48.0 and 47.9 mol.%, respectively), have an average composition of (Fe_1.46Mn_1.45Mg_0.03Ca_0.10)(Al_1.93Ti_0.02)Si_3.01O₁₂ and are comparatively homogeneous in Fe and Mn concentrations from core to rim. Composited garnets from each sample site have δ18O values of 7.2 and 7.4‰. The associated quartz (after tridymite) has δ¹⁸O values of 17.4 and 17.6‰, values indicative of reaction with later, low-temperature water. Unaltered tridymite from higher in the stratigraphic section has a δ¹⁸O of 11.1‰ which, when coupled with the garnet δ¹⁸O values in a quartz-garnet fractionation equation, indicates isotopic equilibration (vapour-phase crystallization) at temperatures of ~600°C. This high-temperature mineralization, formed during cooling of the tuffs, is distinct from the later and commonly recognized low-temperature stage (generally 50–70°C) of calcite, quartz and opal secondary mineralization, formed from downward-percolating meteoric water, that locally coats fracture footwalls and lithophysal floors.