Since the 1960s, mink (Mustela vision) populations in Georgia, North Carolina, and South Carolina have declined, especially in the coastal plain. A prior study suggested that the decline may stem from environmental contaminants. Based on water quality data from each state, we identified 17 substances potentially related to the decline: aldrin, dieldrin, endrin, DDD, DDE, DDT, PCBs, chlordane, alpha-BHC, toxaphene, dibenzofuran, copper, chromium, cadmium, lead, arsenic, and mercury. Mink livers were analyzed for PCB and organochlorine pesticides, and kidneys and femurs were analyzed for metals. Reference sample concentrations from piedmont, mountain, and foothill locations were compared to state coastal plain totals and counties. PCBs for Georgia, dieldrin for South Carolina, and endrin and aldrin for North Carolina were significantly higher than the piedmont reference group. Liver PCB concentrations were higher than those known to cause mink reproductive dysfunction. Mercury concentrations were significantly higher in coastal plain mink from all three states and were in the range of those known to cause impacts to reproduction, growth, and behavior to wild mink. It is unknown what concentrations of cyclodienes cause reduced reproduction or other physiological effects in mink, but the levels reported here probably indicate background concentrations that do not contribute to the decline.