Monodisperse, spherical, polyethylene glycol (PEG)-coated silica nanoparticles have been prepared at room temperature and characterized for the purpose of biomedical applications. The particles were synthesized by the hydrolysis of tetramethyl orthosilicate (TMOS) in alcohol media under catalysis by ammonia, and their size can range from about 50-350 nm in diameter. We studied the particle size and size distribution using a scanning electron microscope (SEM) and an asymmetric field-flow fractionation (AFFF) multiangle static light-scattering instrument. The chemical and/or physical binding of PEG to the silica nanoparticles was studied by infrared spectroscopy, and the weight percentage of PEG attached to the particles was quantified. The PEG-coated silica nanoparticles showed enhanced colloidal stability when redispersed into aqueous solutions from the dried state as a result of the steric stabilization function of the PEG polymer grafted on the surface of particles. A nonspecific protein-binding test was also carried out to show that the PEG coating can help reduce the protein adsorption onto the surface of the particles, relating to the biocompatibility of these PEG-coated particles. Also, the inclusion of magnetic nanoparticles into the silica particles was shown as an example of the possible applications of PEG-coated silica particles. These silica nanoparticles, as a matrix for encapsulation of certain reagents, have potential for applications to in vivo diagnosis, analysis, and measurements inside intact biologic systems.