The application of localized surface plasmon resonance (LSPR) of gold nanoparticles for the detection of biotin-streptavidin binding, as a typical biological reaction, was investigated by using optical waveguide spectroscopy, and two different modes for the use of gold nanoparticles, one as a probe and the other as a label were compared with each other. The combination with optical waveguide spectroscopy was found to bring about a high sensitivity for the biomolecular detection system using LSPR of gold nanoparticles in both modes. In particular, the mode using gold nanoparticles as a label was demonstrated to be of advantage to devising proper procedures for using nanoparticles and evaluating actual response relevant to the phenomenon concerned, and thus to sensitive detection. (C) 2009 Elsevier Inc. All rights reserved.