A new technique to calibrate the sizing and counting characteristics of single-particle optical particle counters (OPCs) is presented. The method is not limited to a specific material for calibration, rather any material that can be aerosolized may be used for calibration. Examples of aerosols with real and complex refractive indices and spherical and non-spherical shapes are employed to demonstrate this calibration approach. The material choices include bis(2-ethylhexyl) sebacate, Fomblin, and soot. To generate monodisperse aerosols, an aerodynamic aerosol classifier is employed along with a constant output atomizer and a miniature inverted soot generator. The optical particle counter is then coupled to a condensation particle counter that facilitates concentration comparisons between the two devices. This approach is useful for OPC calibration for particle sizes less than approximately 5 μm.