Silicon nanowires of different widths were fabricated in silicon on insulator (SOI) material using conventional process technology combined with electron-beam lithography. The aim was to analyze the size dependence of the sensitivity of such nanowires for biomolecule detection and for other sensor applications. Results from electrical characterization of the nanowires show a threshold voltage increasing with decreasing width. When immersed in an acidic buffer solution, smaller nanowires exhibit large conductance changes while larger wires remain unaffected. This behavior is also reflected in detected threshold shifts between buffer solutions of different pH, and we find that nanowires of width >150 nm are virtually insensitive to the buffer pH. The increased sensitivity for smaller sizes is ascribed to the larger surface/volume ratio for smaller wires exposing the channel to a more effective control by the local environment, similar to a surrounded gate transistor structure. Computer simulations confirm this behavior and show that sensing can be extended even down to the single charge level.