Biological functions of most macromolecules depend on their ability to interact with other molecules and a great challenge is the complete description of the protein interaction networks. Biomolecular interaction analysis (BIA) is an optical technology that uses the surface plasmon resonance phenomenon for characterizing macromolecular interactions between an analyte in solution and its ligand immobilized on a sensor chip. Further identification of interacting proteins can be achieved by combining this nondestructive method to mass spectrometry (MS). The BIA-MS approach represents a promising tool in proteomics for the characterization of protein/protein interactions. In this study, we report on the improved sensitivity in the identification of an unknown protein bound to a known ligand by a rapid and simple BIA-MS approach. We took advantage of a new automatic and very reproducible microelution procedure available on BIACORE 3000 instruments, called "microrecovery", to elute the bound protein from the sensor chip. Protein identification was then achieved after tryptic digestion by matrix-assisted laser desorption/ionization-time of flight mass mapping and database search. The strategy was succesfully applied to the model protein SHP2 tyrosine phosphatase interacting with an immunoreceptor tyrosine-based inhibitory motif sequence of the sst2 somatostatin receptor. Optimization of the BIA-MS approach allowed the unambiguous identification of 10-20 fmol of the protein specifically trapped from a complex mixture of cytosolic extracts.