Closely located domestic and public supply wells were sampled using identical sampling procedures to allow comparison of water quality associated with well type. Water samples from 15 pairs of wells with similar screened intervals completed in the central High Plains regional aquifer in parts of Kansas, Oklahoma, and Texas were analyzed for more than 200 water quality constituents. No statistically significant differences were observed between the concentrations of naturally-derived constituents (major ions, trace elements, and radon) in paired wells. However, differences in water quality between paired wells were observed for selected anthrepogenic compounds (pesticides and tritium), in that some public supply wells produced water that was more recently recharged and contained constituents derived from surface activities. The presence of recently recharged water and compounds indicative of anthrepogenic activities in some public supply wells was likely due to operational variations (pumping rate and pumping cycles), as demonstrated in a particle tracking simulation. Water containing surface-derived anthropogenic compounds from near the water table was more quickly drawn to high volume public supply wells (less than five years) than domestic wells (greater than 120 years) with small pumping rates. These findings indicate that water quality samples collected from different well types in the same area are not necessarily directly comparable. Sampling domestic wells provides the best broad-scale assessment of water quality in this aquifer setting because they are less susceptible to localized contamination from near the water table. However, sampiing public supply wells better represents the quality of the used resource because of the population served.