Since its first crystallization, the aqueous structure of the tellurium-containing experimental drug AS-101 has never been studied. We show that, under the aqueous conditions in which it is administered, AS-101 is subjected to an immediate ligand-substitution reaction with water, yielding a stable hydrolyzed oxide anion product that is identified, for the first time, to be TeOCl3-. Studying the structure of AS-101 in propylene glycol (PG), an alcoholic solvent often used for the topical and oral administration of AS-101, revealed the same phenomenon of ligand-substitution reaction between the alcoholic ligands. Upon exposure to water, the PG-substituted product is also hydrolyzed to the same tellurium(IV) oxide form, TeOCl3-.