Diethyl dithiocarbamate (DDC) was used to inhibit the copper- and zinc-containing superoxide dismutase (Cu,ZnSOD) of Escherichia coli in order to expose its physiological function, DDC inhibited the aerobic growth of a sodA sodB mutant much more than it did the growth of a SOD-replete parental strain and this inhibitory effect was oxygen-dependent. The SOD mimic MnTMPyP markedly diminished the growth inhibitory effect of DDC, Transfer of the sodA sodB strain from anaerobic to aerobic conditions induced fumarase C, which is a member of the soxRS regulon, DDC augmented this induction, These results indicate that the Cu,ZnSOD provides a defense against oxidative stress, which is more important to the sodA sodB mutant than to its SOD-replete parental strain. (C) 1996 Academic Press, Inc.