An effective and reproducible method of preparing highly monodisperse organic-inorganic hybrid silica spheres was studied. One process, one precursor (organosilane) and one solvent (water) were used in our experiments. The size of hybrid silica spheres could be adjusted from 360 to 770 nm with relative standard deviation below 2% by controlling the concentration of the organosilane precursor and the ammonia catalyst. The increasing of the precursor concentration increases the particle size while the catalyst concentration has a reverse effect on the particle size. The concept of homogeneous nucleation and growth processes are introduced to explain the formation mechanism and the effect of reaction conditions. The scanning electron microscopy (SEM) images illustrate the copiousness in quantity and the uniformity in size/shape of the particles that could be routinely accomplished in this synthesis. Fourier transform infrared (FT-IR) and Si-29 nuclear magnetic resonance (NMR) spectra confirm the structure of vinyl hybrid silica spheres, where the vinyl group (-CH=CH2) exists and connects to the silicon atom. This method has also been extended to design and prepare other organic-inorganic hybrid materials especially in monodisperse surface-modified silica spheres. (C) 2008 Elsevier Inc. All rights reserved.