Concentrations of 18O and deuterium in ground waters beneath the Hanford Reservation, Washington State, suggest that the meteoric waters recharging the basalt aquifers have been progressively depleted in these isotopes since at least Pleistocene time. This conclusion is supported by oxygen-isotope analyses of low-temperature secondary minerals filling vugs and fractures in the basalts, which are used to approximate the 18O content of ground water at the time the mineral assemblage formed. A fossil profile of δ18O values projected for ground water in a 1500 m vertical section beneath the reservation suggests that the vertical mixing of shallow and deep ground water indicated by present-day hydrochemical data was also occurring during Neogene time. These data also suggest that a unidirectional depletion of 18O and deuterium recorded in Pleistocene ground waters may have extended considerably further back in time. This shift is tentatively attributed to the orographic depletion of 18O associated with the progressive uplift of the Cascade Range since the middle Miocene.