The effects of dietary copper deprivation on the activities, immunoreactive protein concentrations, and mRNA abundance of copper/zinc- and manganese-superoxide dismutase (Cu/Zn- and Mn-SOD) were examined in liver, heart, and brain of weanling rats fed a Cu-deficient diet for 4 weeks. Hepatic Cu/Zn-SOD activity, enzyme content, and mRNA abundance were significantly reduced, and, conversely, the activity, protein, and mRNA levels of Mn-SOD were significantly elevated in Cu-deficient rats. In Cu-deficient heart, the activity and protein content for Cu/Zn-SOD were reduced, whereas those for Mn-SOD were increased; the levels of mRNAs for these two enzymes was unaffected. Dietary Cu deficiency was without effect on the activities, enzyme contents, and mRNA abundance of brain Cu/Zn- and Mn-SOD. These results indicate that SODs from liver, heart, and brain exhibit differential sensitivities to dietary Cu deprivation, and that different mechanisms (transcriptional, posttranscriptional, or posttranslational) may be involved in their regulation.