Submicron particles of megestrol acetate (MA) were precipitated by rapid expansion of supercritical solution (RESS) method, using CO2 as supercritical solvent in the presence of menthol as solid co-solvent. The effects of extraction temperature, extraction pressure and weight fraction of menthol on the mean particle size of precipitated particles were investigated using full factorial design. The experiments were carried out at three temperature levels from 40 to 60 degrees C, three pressure levels from 15 to 25 MPa, and 2 to 6 wt.% of co-solvent. Megestrol acetate nanoparticles were formed with mean particle sizes between 102.8 and 516.3 nm and statistical analysis showed that pressure had the most considerable effect on the size of nanoparticles. Increasing the temperature and pressure, and decreasing the amount of solid co-solvent resulted in the formation of finer particles. (C) 2012 Elsevier B.V. All rights reserved.