The effect on copper status of diets containing homocysteine, an intermediate in the transsulfuration pathway of methionine metabolism, was investigated in rats. Two groups of six male weanling Sprague-Dawley rats were provided with deionized water and pair-fed diets that were adequate (14.0 mg/kg) or deficient (1.3 mg/kg) in Cu to groups fed diets similarly adequate or deficient in Cu but containing DL-homocysteine (10 g/kg). Hemoglobin concentration, tissue Cu levels and the activities of the Cu-dependent enzymes--ceruloplasmin, superoxide dismutase and cytochrome c oxidase--were markedly lowered by Cu-deficient diets and by homocysteine. These dietary treatments also lowered the activity of glutathione peroxidase and produced concomitant increases in the activity of manganese-dependent superoxide dismutase and iron levels in the liver. However, dietary homocysteine decreased hepatic Mn and low Cu diets decreased cardiac iron content. Moreover, both dietary treatments significantly lowered kidney Fe levels. Homocysteine increased heart, liver and kidney weights (g/100 g body tissue) and greatly elevated the level of thiobarbituric acid reactive substances (TBARS) in heart tissue. These results indicate that dietary homocysteine can markedly lower Cu status in rats and result in tissue redistribution of Fe and increased cardiac levels of TBARS, a measure of lipid peroxidation.