To study interaction of arsenic with proteins, we have developed an affinity selection technique, coupled with mass spectrometry, to select and identify specific arsenic-binding proteins from a large pool of cellular proteins. Controlled experiments using proteins either containing free cysteine(s) or inactive cysteine showed that the arsenic affinity column specifically captured the proteins containing free cysteine(s) available to bind tu arsenic .The technique was able to capture and identify trace amounts of bovine biliverdin reductase B present as a minor impurty in the commercial preparation of carbonic anhydrase II ,demonstrate the ability to identify arsenic-binding proteins in the presence of a large excess of non-specific proteins. application of the technique to the analysis of subcellular fractions of A549 human lung carcinoma cells identified 50 proteins in the analysis of subcellular fraction ,and 24 proteins in the membrane/ organelle fraction that could bind to arsenic .This added substantially to the current list of only a few known arsenic-binding proteins.