A new refractometer has been developed based on changes in the effective refractive index (RI) of the highest-order TE (or TM) mode in a prism-coupled multimode planar waveguide induced by interaction between an evanescent field and a liquid sample. The waveguide was a 100-mu;m -thick quartz plate fixed on a poly(methyl methacrylate) support containing a flow cell. A pair of prism couplers contacted the quartz plate in the flow-cell region. Such an optical sensor can detect the RI of liquid in a wide range by monitoring the resonant angle of the highest-order mode that changes order number with changes in the sample's RI. When a highest-order mode corresponding to a given RI range is used as the sensor probe, a slight RI change in this range can be detected by measurement of the output light intensity. With this method the sensor was demonstrated to have a resolution of 3x10(-5) for the RI of an aqueous solution. Combining this result with theoretical calculation indicates that the sensor can detect a 0.5-nm-thick monolayer adsorbed from an aqueous solution. Therefore, the sensor is suitable for real-time detection of biomolecular interactions.