Sodium perchlorate forms a reversible and enzymatically inactive complex with human red blood cell catalase. The rates of binding and association constants increase inversely with pH. Analysis of the dependence of association constants on pH suggests participation of a carboxylate or imidazole group in the proton-assisted binding of perchlorate to catalase. Formation of the complex resulting from binding of perchlorate to the apoprotein involves a conformation change and is accompanied by alterations in the optical spectrum of catalase. In the presence of hydrogen peroxide the progressive inhibition of the enzyme by perchlorate is faster than at nonturnover conditions, indicating additional reaction of the ligand with catalase intermediate complexes.