In derepressed yeast cells the cytoplasmic malate dehydrogenase activity disappears after addition of glucose to the culture medium. Using specific antisera, it seemed possible to isolate an inactive enzyme protein if the inactivation resulted from an allosteric inhibition or from a chemical modification. The present studies show that after the inactivation an inactive enzyme protein is immunologically not detectable. Together with the irreversibility of the inactivation in vivo and in vitro this result supports a proteolytic mechanism of enzyme inactivation.