We have developed a highly sensitive refractometric sensor based on fused silica microsphere resonators. The spectral position of the whispering gallery mode (WGM) of a sphere shifts in response to the refractive index change in the surrounding medium. The strong light-matter interaction due to the extremely high Q factor associated with the WGM results in a sensitivity of approximately 30 nm/RIU (refractive index units). This, together with the high spectral resolution of our sensor system (similar to 0.01 pm), yields a detection limit of refractive index change on the order of 10(-7) RIU. Theoretical calculation is also performed and agrees well with the experimental data. (C) 2005 American Institute of Physics.