The particle size of organic and inorganic materials is vital parameter to determine its final use. Most of the newly developed pharmaceutical materials are poorly soluble or insoluble in the aqueous media such as biological fluids. Particle size reduction of such pharmaceuticals is one of the clues to improve the dissolution rate, adsorption and bioavailability. In this study, the effect of extraction and expansion parameters of the RESS process such as extraction temperature (313-333 K), extraction pressure (140-230 bar), effective nozzle diameter (450-1700 mu m), nozzle length (2-15 mm) and spraying distance (1-7 cm) on the size and morphology of the precipitated particles of cephalexin were investigated. The morphology and particle size of the unprocessed and processed (precipitated) particles were examined by the SEM images. The mean particle size of the precipitated particles was between 0.86 and 7.22 mu m depending upon the different experimental conditions used. The precipitated cephalexin particles were close to spherical form while the unprocessed particles were irregular or needle in shape. (C) 2010 Elsevier Ltd. All rights reserved.