Tissue injury by Aspergillus niger infection is associated with the deposition of calcium oxalate crystals. Oxalate is recognized to function as a ligand for numerous metal cations and will react with ferric ion to form a coordination complex. We describe oxalate deposition in the lung of a patient with A. niger infection and quantify surface-complexed Fe3+. Crystals collected from lung tissue demonstrated considerable concentrations of surface iron. In addition, we tested the hypothesis that this surface coordination of Fe3+ by oxalate is associated with increased in vitro oxidant generation. Calcium oxalate crystals (1.0 mg/ml) complexed all available Fe3+ from solutions of ferric chloride to concentrations of as much as 1.0 mM. Oxidant generation in both a chemical and a cellular system, measured as thiobarbituric-acid-reactive products of deoxyribose and chemiluminescence, respectively, increased with coordination of higher concentrations of inorganic iron. We conclude that calcium oxalate associated with A. niger infection complexes iron cations onto the crystalline surfaces and may generate oxidants at the solid-solution interface, which could result in tissue injury.