Mercuric and cupric ions have been found to inactivate the cellulolytic activity of the cellulase (1,4-(1.3;1,4)-β- d-glucan-4-glucanohydrolase; endoglucanase; EC 3.2.1.4) from Schizophyllum commune in a time-dependent manner. Partial recovery of enzymatic activity could be achieved by chelation only in the presence of a chaotropic reagent. Semi-logarithmic plots of residual activity versus time were biphasic and could be resolved into two first-order processes, suggesting the formation of a partially inhibited enzyme and its subsequent slower conversion to an inactivated form. Second-order rate constants for the slower process leading to enzyme inactivation were calculated to be 4.62 and 9.24 · 10 −2 M −1 · s −1 for Hg 2+ and Cu 2+, respectively. The binding of a competitive inhibitor, cellobiose, prior to metal addition protected the enzyme from rapid inactivation in a concentration-dependent manner. By both ultraviolet absorption and flurorescence spectroscopy, the mercuric ions were shown to interact with tryptophan residues of the enzyme. It is proposed that metal inactivation of the cellulase proceeds by chelation involving carboxylates at the active centre, thereby perturbing the tryptophan residue(s) in the binding site of the enzyme.