Escherichia coli strains harboring trans-acting mutations affecting the expression of Mn-superoxide dismutase (SOD) gene (sodA) were used to study sodA regulation. Complementation studies revealed that either arc (aerobic respiratory control) or fur (ferric uptake regulation) loci independently complemented anaerobic expression of a sodA:: lacZ protein fusion in one mutant strain (UV16). This mutant exhibited phenotypes (i.e., elevated outer membrane proteins, enzyme activity, and dye sensitivity) typical of fur and arc mutants. When these mutations were introduced into an otherwise wild-type background, anaerobic sodA expression occurred only when both arc and fur mutations were present simultaneously, suggesting cooperative roles of Fur and Arc in sodA repression. The reconstructed fur arcA and fur arcB double mutants were still inducible by iron chelators, suggesting the possible involvement of another iron-containing repressor protein. A second independent mutant strain harboring a trans-acting regulatory mutation (UV14) was only partially complemented by multicopy plasmids carrying fur+ or arc+ genes, implicating other genetic elements in sodA regulation.