Poly(D,L-lactide-co-glycolide) (PLGA) biodegradable microspheres with gentamicin for local treatment of microbial bone infection were prepared and characterized. Gentamicin was assayed spectrophotometrically at 332 nm after derivation with the o-phthalaldehyde; biodegradable polymers studied did not interfere with this method of gentamicin analysis. PLGA microspheres were made by the double emulsion solvent evaporation method with modifications. The first W(1)/O emulsion was obtained by ultrasonication or high-speed homogenization, and a large aqueous phase W(2) (200 ml) was used. The ultrasonication method increases the microsphere percentage observed in the 20-40 microm size range and, in all cases SEM-microphotographs revealed homogeneous and spherically shaped particles with smooth surfaces. The method including ultrasonication proposed in the present work improved the encapsulation efficiency of gentamicin by nearly 100% (97.94%). Several mathematical models based on heterogeneous hydrolytic degradation were applied to evaluate their suitability in describing gentamicin released from PLGA microspheres. Two models, one of them including an autocatalytic process, were finally proposed to contribute to understand the mass transport mechanism involved in drug release from these microspheres.