The aim of this study was to better understand the underlying drug release mechanisms in poly(lactic-co-glycolic acid) (PLGA) microparticles in which the drug is dispersed in the form of tiny particles ("monolithic dispersions"). Differently sized diprophylline-loaded microparticles were prepared using a solid-in-oil-in-water solvent extraction/evaporation technique. The microparticles were characterized before and after exposure to phosphate buffer pH 7.4 at 4, 20 and 37 °C. In vitro drug release was measured from ensembles and single microparticles. GPC, DSC, SEM, gravimetric analysis, drug solubility measurements and optical microscopy were used to elucidate the importance of polymer swelling & degradation, drug dissolution and diffusion. The diprophylline was initially homogeneously distributed throughout the microparticles in the form of tiny crystals. The burst release (1st phase) was strongly temperature-dependent and likely attributable to the dissolution of drug crystals with direct surface access (potentially via tiny pores). The about constant release rate during the 2nd phase also strongly depended on the temperature. It can probably be explained by the dissolution of drug crystals in surface near regions undergoing local swelling. During the observation period, the 3rd (again rapid) drug release phase was only observed at 37 °C, and seems to be caused by substantial PLGA swelling throughout the entire microparticles. This phase starts as soon as a critical polymer molecular weight of about 25 kDa is reached: Significant amounts of water penetrate into the systems, dissolving the remaining diprophylline crystals and substantially increasing the mobility of the dissolved drug molecules. Thus, this study provides additional experimental evidence (obtained at lower temperatures) confirming the hypothesized root causes for drug release from PLGA microparticles containing dispersed drug particles.