The system dextran-DMSO-CO2 has been chosen as a model system to study the fundamentals of the precipitation of biodegradable polymers, using the precipitation with a compressed antisolvent (PCA) process. At conditions of completely miscibility between the organic solvent (DMSO) and CO2, it is proposed that the formation of droplets in the system is not the consequence of atomization of the DMSO solution, but rather the result of the occurrence of a liquid-liquid phase split when the DMSO-solution and CO2 are intimately mixed. Penetration of CO2 into the droplets and stripping of DMSO induces the solidification of these droplets. A new device was designed to separate the three steps involved in the process: mixing of CO2 and solution, liquid- liquid phase split, and stripping of the solvent. This new device eliminates agglomeration of particles, and yields reproducible results. The particle size can be easily manipulated over a size range from several nanometers to tenths of microns by changes in the operating conditions. The influence of these operating conditions (pressure, temperature, polymer concentration, and solution/CO2 composition ratio) on particle morphology has been studied. (C) 2004 American Institute of Chemical Engineers.