Aerobic incubation of Halobacterium halobium with low concentrations of cyanide or azide resulted in a twofold increase in activity of the Mn-containing superoxide dismutase (SOD). A similar effect was observed with antimycin A, albeit at a higher concentration. Oxygen consumption increased 100% at concentrations of cyanide, azide, and antimycin A that produced maximal SOD induction. Luminol chemiluminescence of H. halobium cells, indicative of oxidative activity, was elevated in the presence of concentrations of aerobic respiratory inhibitors that corresponded to maximal levels of SOD induction. In addition, oxidation of NADH by cell extracts was maximal at inhibitor concentrations that correlated with the peak induction of SOD. Proton fluxes for H. halobium cells also corresponded to concentration ranges of inhibitor resulting in greatest SOD levels, indicative of a potential uncoupling effect. A similar phenomenon was also observed with the uncoupler carbonyl cyanide m-chlorophenyl hydrazone. Growth was unaffected by inhibitors at the concentrations used for SOD induction. The results are interpreted as an induction of enhanced levels of SOD through a combination of increased electron flow and an increased oxidative environment.