Methyl methacrylate (MMA), methoxy poly (ethylene glycol) monomaleate (MPEG), and acrylamidoglycolic acid (AGA) terpolymeric microgels (MGs) have been synthesized by free-radical surfactant-free emulsion polymerization. MPEG was synthesized from maleic anhydride and methoxy poly(ethylene glycol). The MGs were crosslinked with ethylene glycol dimethacrylate, and the chemical crosslinking was confirmed by Fourier transform infrared spectroscopy. 5-Fluorouracil (5-FU), a model anticancer drug, has been loaded into the MGs by in situ and adsorption methods. Empty as well as drug-loaded MGs were then characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). DSC and XRD studies indicated a molecular level dispersion of the drug in PMMA MGs during in situ loading. TEM images showed the formation of spherical MGs. In vitro release of 5-FU from the crosslinked poly(MMA-co-AGA-co-MPEG) MGs were investigated at both PH 7.4 and 1.2 buffer medium that controlled release of the drug LIP to similar to 18 h. Both the encapsulation efficiency and the release patterns were dependent on the amount of crosslinking agent and the amount of drug loaded. (C) 2008 Wiley Periodicals, Inc. J Appl Polym Sci 111: 845-853, 2009