The exposure of white-footed mice (Peromyscus leucopus) to lead and cadmium and the potential associated toxic effects were examined at three sites contaminated with lead in the Southeast Missouri Lead Mining District and at a reference site. Mice from the contaminated sites showed evidence of oxidative stress and red-blood cell δ-aminolevulinic acid dehydratase (ALAD) activity was depressed by an average of 68% at the most contaminated site. However, histological examinations of the liver and kidney, cytologic examination of blood smears and biomarkers of lipid peroxidation and DNA damage failed to show evidence of toxic effects from lead. The biomagnification ratio of cadmium (hepatic concentration/ soil concentration) at a site with a strongly acid soil was 44 times the average ratio from two sites with slightly alkaline soils. The elevated concentrations of cadmium in the mice did not cause observable toxicity, but were associated with about a 50% decrease in expected tissue lead concentrations and an increase in ALAD activity compared to the reference. Lead was associated with a decrease in concentrations of hepatic glutathione and thiols, whereas cadmium was associated with an increase. Relying on a tissue-based approach, we calculated regressions relating both dietary exposures and tissue concentrations of lead to concentrations of lead in soil.