This paper describes the use of a modified electrospray technique to prepare quasi-monodisperse and size-controllable poly(lactic-co-glycolic acid) (PLGA) aerosol particles with matrix-distributed rifampicin (RIF). These microparticles can be facilely synthesized by electrospraying a RIF/PLGA solution using a cone-jet mode, and then the sprayed microparticles go through a size separation process during which microparticles move to a collector to obtain desirable quasi-monodisperse microparticles. Experiment shows that the microparticle size can be well controlled by the jet flow rate, following the scaling laws of electrospray. The microparticle morphologies demonstrated are closely related to the drug loading quantity. A low drug loading produces the microparticles with spherical shape. With an increase of drug loading, wrinkled microparticles emerge. The drug release results indicate that drug release profiles are closely related to the microparticle diameter and drug loading. The concentration gradient of RIF in the particle matrix decreases outwards from some position as the microparticle diameter increases but rises with the increase of RIF loading. The as-sprayed quasi-monodisperse aerosol particles with mean diameters in the range of 2-5 mu m have potential application for pulmonary drug delivery. (c) 2008 Elsevier Ltd. All rights reserved.