The Cu/Zn superoxide dismutase activity of Saccharomyces cerevisiae was found to be strictly related to the extent of oxygen metabolism, since cells grown under anaerobic or repressed conditions were found to contain 10% and 40% the activity of derepressed cells, respectively. The dependence of Cu/Zn superoxide dismutase on oxygen was found to be related to the availability of copper to the cells since the enzyme activity and immunoreactive protein measured under the various conditions was roughly proportional to the copper content of cells and in anaerobic cells a large fraction of the enzyme was found to be in the form of an inactive proenzyme which was activated by the addition of copper to cell extracts. The Cu/Zn superoxide dismutase mRNA did not parallel the dependence of the enzyme concentration on oxygen metabolism, suggesting that the gene expression was affected by copper also at the post-transcriptional level. However, under conditions of copper overloading, a more direct effect on transcription was observed and the presence of the inactive proenzyme in anaerobic cultures was associated with the over-expression of metallothionein.