A program of research is proposed to develop immunospecific sensors for use with surface enhanced Raman (SER) spectroscopy for a direct approach to immunoassay. The Phase I objective is to demonstrate that sufficient difference(s) exist between SER spectra of an antibody (Ab) molecule, its complementary antigen (Ag), and the Ab/Ag complex to provide a basis for development of SER immunosensors. The experimental program consists of three tasks: 1) evaluate the SER spectra of individual Abs and their Ags adsorbed onto surfaces which give enhanced Raman activity; 2) evaluate SER spectra of Ab/Ag complexes to identify unique spectral features associated with the complex; 3) evaluate SER spectra of Abs linked to SER substrate while being exposed to solution containing complementary Ag. In situ observation of spectral changes during Ab/Ag binding would provide an additional mode of analysis as well as provide information regarding kinetics of Ab/Ag complex formation. The spectroscopic approach offers innovation over present methods of immunoassay in that it may provide instantaneous measurement of Ab/Ag binding and reagentless operation.