Lignocellulosic biomass is an underutilized, renewable resource that can be converted to biofuels. The key step in this conversion is cellulose saccharification catalyzed by cellulase. In this work, the effect of metal ions on cellulose hydrolysis by cellulases from Penicillium decumbens was reported for the first time. Fe3+ and Cu2+ were shown to be inhibitory. Further studies on Fe3+ inhibition showed the inhibition takes place on both enzyme and substrate levels. Fe3+ treatment damages cellulases' capability to degrade cellulose and inhibits all major cellulase activities. Fe3+ treatment also reduces the digestibility of cellulose, due to its oxidation. Treatment of Fe3+-treated cellulose with DTT and supplementation of EDTA to saccharification systems partially relieved Fe3+ inhibition. It was concluded that Fe3+ inhibition in cellulose degradation is a complicated process in which multiple inhibition events occur, and that relief from Fe3+ inhibition can be achieved by the supplementation of reducing or chelating agents. (C) 2013 Elsevier Ltd. All rights reserved.