The microstructure of three types of UASB granules respectively treating sucrose, glutamate and brewery wastewaters in mesophilic conditions were analyzed by light, scanning electron and transmission electron microscopies, along with the specific methanogenic activity (SMA) of the granules. Results showed that the granule's microstructure was dependent on the nature of the substrate. Those degrading soluble carbohydrates exhibited a layered structure, while those degrading glutamate exhibited a rather uniform structure. Such a difference was explained based on the substrate's rates of acidogenesis and diffusion. A model of the typical layered structure was proposed. In addition, the acetoclastic Methanothrix was found as the key structural element in all the granules, suggesting that it plays an important role in granulation. Three types of syntrophic microcolonies were found to be abundant in granules degrading soluble carbohydrates: two were juxtapositioned syntrophic microcolonies, each was composed of hydrogen-producing acetogens and hydrogen-consuming methanogens, while the third was a cluster-type of syntrophic association between two microcolonies. The SMA data using individual VFA as substrate provided supporting evidence to the observations of the bacterial compositions in the granules.