The level of manganese superoxide dismutase (MnSOD) as determined by an immunoreactive assay was reduced in human cancer cells. The reduced amount of immunoreactive MnSOD in these cells was observed regardless of the growth state of the cells. The decrease in the enzyme protein was associated with a decrease in the mature form of MnSOD transcript as determined by Northern Analysis. The decreased amount of the mature form of MnSOD transcript was accompanied by an increase in the amount of the partially processed form of MnSOD transcript. These results suggest that RNA processing or translation of MnSOD mRNA may be responsible for the decreased amount of MnSOD activity in human tumor cells.