Microparticles of the anticancer drug 5-fluorouracil (5-Fu) were successfully prepared by supercritical antisolvent (SAS) precipitation using dimethylsulfoxide as solvent. The effect on particle size (PS) of the experiment parameters was studied. The conditions of temperature and pressure were the most important factors. Mean PS values ranged from 220 to 670 nm. Using as solvent a dimethylsulftudde + dichloromethane mixture, the SAS process was also used to obtain composite particles in which 5-Fu crystals are coated by a layer of poly(L-lactide) spheres. The particle morphology was studied by SEM. Other characterization included powder X-ray diffraction, DSC, TGA, and the measurement of the dissolution profiles. The composite particles were shown to provide a controlled delivery system.