A survey was conducted in 1975–1976 to determine the background levels of lead, cadmium, and mercury in tissues of healthy swine, cattle, dogs, and horses from the midwestern United States. Blood, muscle, liver, and kidney were assayed from cattle and swine slaughtered at federal meat inspection plants and in dogs and horses obtained from local pounds and sales barns. A total of 959 samples for lead, 972 samples for cadmium, and 827 samples for mercury were analyzed. The maximum muscle lead concentration was less than 0.10 ppm in dogs and horses. Fourteen percent of the cattle muscle samples contained between 0.16 and 0.34 ppm lead. The blood lead concentration was generally lower than 0.10 ppm in cattle, swine and horses; however, in dogs 44% of the blood lead values were between 0.11 and 0.37 ppm. The liver and kidney lead content was generally less than 0.50 ppm in all species, and the maximum lead content detected in either tissue was less than 2.0 ppm. Elevated tissue levels of cadmium were observed in horses as compared to other species. While the maximum muscle cadmium content in cattle, swine, and dogs rarely exceeded 0.05 ppm, levels in excess of 0.06 ppm were found in all the 19 horse muscle samples. Blood cadmium levels in all species were near or below the detection limit of 0.005 ppm. The median cadmium concentration in liver and kidney was below 0.2 and 0.6 ppm, respectively, in cattle, swine, and dogs. However, in horses the median concentration was 20 times greater in liver and 4 times higher in kidney. The mercury concentrations in muscle and blood of all species were near or below the detection limit of 0.02 ppm. The median concentrations of mercury in liver and kidney, respectively, were: 0.02 ppm each in swine and cattle; 0.02 ppm and 0.05 ppm in dogs; and 0.12 ppm and 0.72 ppm in horses. The results suggest that exposure of animals to dietary or environmental lead, cadmium, and mercury in the midwestern United States is not significant. The specific cumulation of cadmium and mercury in tissues of horses suggests the need to explore the role these metals play in selective biological processes.