Hemin (ferriprotoporphyrin IX-chloride) can mediate the covalent cross-linking and degradation of yeast glutathione reductase. This reaction requires both NADPH and oxygen suggesting the involvement of a reduced oxygen species in the cross-linking and degradation process. During the course of the reaction the enzymatic activity of glutathione reductase is rapidly destroyed. Implications of these findings for a regulatory role of hemin in cell biology are discussed.