Specific and selective protease inhibitors are potentially powerful tools in clinical therapy. These inhibitors could be used to inactivate the target proteases in the pathogenic processes of human diseases such as emphysema, arthritis, pancreatitis, thrombosis, high blood pressure, muscular dystrophy, cancers, AIDS, and many others1 ~3).During our screening for biologically active compoundsfrom marine sources, a strain of the fungus Microascus longirostris was found to produce secondary metabolites that strongly inhibited cysteine proteases. Bioassay-guided fractionation of the methanolic extract of the mycelia led to the isolation of three potent protease inhibitors. Based on spectroscopic data obtained from these three compounds,we have identified them as the epoxysuccinates 1, 2 and 3. While this work was being completed, another research group4) reported the isolation of compounds1 and 2, or cathestatins B and A respectively, from a different fungal source (Penicillium citrinum). In this paper, we describe the production, isolation, structure determination, and inhibitory activities of cathestatins A and B (2, 1), and of cathestatin C (3), a new and unreported member of this class of compounds.