Radiocarbon, δ13C and major-element data were used to construct a geochemical framework for interpretation of the hydrological flow system in the lower San Pedro basin, southeastern Arizona, USA. The 14C and major-element data show a regional confined aquifer that extends throughout most of the basin. Groundwater ages, after correcting for chemistry, are greater than 10 ka bp. The groundwater ages do not increase in a downvalley direction, the assumed direction of groundwater movement in most intermontane basins in the region, but along general flow paths normal to the mountains toward the center of the basin. Recharge to the confined aquifer originates from infiltration of precipitation and runoff near the alluvium-mountain contact along the Galiuro Mountains and is discharged by evapotranspiration along the center of the basin. The hydrogeological concept of the 14C model is supported by the water chemistry and by the mass transfer defined by the chemical model. Weathering of primary silicate minerals in the confined aquifer does not occur downvalley, but only along the direction of flow. Hydraulic conductivities calculated for the aquifer from 14C velocities are about an order of magnitude slower than those determined through hydrological methods. The lower hydraulic-conductivity values are attributed to a thick confining layer overlying the discharge area along the San Pedro River.