The analysis of emerging contaminants in natural water sources has been based primarily on the analysis of “known unknowns”. These are compounds whose identities are known and several of their chemical or physical properties are tabulated in a database. Here we present an analytical strategy for the determination of pollutants with unknown structures based on liquid chromatography and full scan tandem mass spectrometry with detection based on structural features that suggest the potential toxicity of the unknown. We are using precursor ion scanning for m/z 35 and m/z 37 ions that are specific for chlorine-containing compounds. Precursor ion scanning for chloride ions is carried out over consecutive, narrow mass ranges using several injections. The identification of unknown compounds is facilitated by accurate mass and product ion determinations of the chlorinated compounds detected during precursor ion analyses. Ultimately, the unknown chlorinated compound is identified by comparing its spectroscopic characteristics and retention time with analytical standards suggested to have the same empirical formula as the unknown. This experimental strategy is demonstrated by the identification of a dichlorinated sulfonic acid (3,5-dichloro-4-hydroxybenzenesulfonic acid) that has been detected in several branches of the Chicago River and Chicago wastewater effluent.