The relation between sinkhole density and water quality was investigated in seven selected carbonate aquifers in the eastern United States. Sinkhole density for these aquifers was grouped into high (>25 sinkholes/100 km²), medium (1–25 sinkholes/100 km²), or low (<1 sinkhole/100 km²) categories using a geographical information system that included four independent databases covering parts of Alabama, Florida, Missouri, Pennsylvania, and Tennessee. Field measurements and concentrations of major ions, nitrate, and selected pesticides in samples from 451 wells and 70 springs were included in the water-quality database. Data were collected as a part of the US Geological Survey (USGS) National Water-Quality Assessment (NAWQA) Program. Areas with high and medium sinkhole density had the greatest well depths and depths to water, the lowest concentrations of total dissolved solids and bicarbonate, the highest concentrations of dissolved oxygen, and the lowest partial pressure of CO₂ compared to areas with low sinkhole density. These chemical indicators are consistent conceptually with a conduit-flow-dominated system in areas with a high density of sinkholes and a diffuse-flow-dominated system in areas with a low density of sinkholes. Higher cave density and spring discharge in Pennsylvania also support the concept that the high sinkhole density areas are dominated by conduit-flow systems. Concentrations of nitrate-N were significantly higher (p < 0.05) in areas with high and medium sinkhole density than in low sinkhole-density areas; when accounting for the variations in land use near the sampling sites, the high sinkhole-density area still had higher concentrations of nitrate-N than the low sinkhole-density area. Detection frequencies of atrazine, simazine, metolachlor, prometon, and the atrazine degradate deethylatrazine indicated a pattern similar to nitrate; highest pesticide detections were associated with high sinkhole-density areas. These patterns generally persisted when analyzing the detection frequency by land-use groups, particularly for agricultural land-use areas where pesticide use would be expected to be higher and more uniform areally compared to urban and forested areas. Although areas with agricultural land use and a high sinkhole density were most vulnerable (median nitrate-N concentration was 3.7 mg/L, 11% of samples exceeded 10 mg/L, and had the highest frequencies of pesticide detection), areas with agricultural land use and low sinkhole density still were vulnerable to contamination (median nitrate-N concentration was 1.5 mg/L, 8% of samples exceeded 10 mg/L, and had some of the highest frequencies of detections of pesticides). This may be due in part to incomplete or missing data regarding karst features (such as buried sinkholes, low-permeability material in bottom of sinkholes) that do not show up at the scales used for regional mapping and to inconsistent methods among states in karst feature delineation.