Annexin III, a putative inositol (1,2)-phosphohydrolase, was co-crystallized with inositol 2-phosphate, the inhibitor of the reaction, and its structure was solved to 1.95 A resolution. No enzyme active site was observed in the structure. Assays for enzymatic activity were also negative. Search for annexin III-inositol phosphate interactions using the BIAcoreTM system revealed an affinity for inositol cyclic (1,2)-phosphate, suggesting annexin III may sequester the molecule in the cell. The BIAcoreTM system used with different phospholipids showed that annexin III displays specificity for phosphatidylethanolamine, but not for phosphatidylinositols. Interestingly, a molecule of ethanolamine was found bound to the protein in the crystal structure. Coupled with the fact that this is a particularly abundant phospholipid in granules specific to neutrophils, cells where annexin III is highly expressed, our finding could be pointing to a physiological role of annexin III.