The effect of processing techniques on the molecular weight of the polymer in biodegradable microspheres of poly(dl-lactic acid) (PLA) and poly(dl-lactic-co-glycolic acid) (PLGA) was investigated. Multiphase microspheres were produced by conventional agitation, potentiometric dispersion, or sonication. Gel permeation chromatography was used to determine the molecular weight of the polymer before and after processing. Polymer in microspheres of PLA produced by sonication experienced a 21% decrease in molecular weight of the polymer after 90 s of sonication, while microspheres made by potentiometric dispersion or mechanical agitation exhibited insignificant changes in molecular weight. Microspheres produced by potentiometric dispersion were found to have a more narrow particle size distribution compared to the other methods. A decrease in the internal diameter of the infusion tube used to produce multiphase microspheres by the potentiometric dispersion method was found to decrease the mean particle size of the resultant microspheres. Two surfactants were investigated at varied levels for utilization in the continuous phase, and particle size analysis revealed that increased surfactant levels caused an increase in the mean particle size of microspheres containing BSA produced by potentiometric dispersion. This phenomenon was attributed to an increase in conductivity of the continuous phase as the surfactant level was increased.