The characteristics of granular sludge from full-scale upflow anaerobic sludge blanket reactors used for the treatment of brewery wastewater were investigated. Fluorescence in situ hybridization (FISH) analyses of settled granules from a reactor that had been treating brewery wastewater stably at COD removal rates of over 90% for more than 6 months showed that a methanogen of the genus Methanosaeta was predominant near the granule surface and that Bacteria were not abundant. The center of the granules was composed of dead or resting cells, or both, which were used as a support for active archaeal and bacterial cells near the surface. Periodic analysis of granules from full-scale plants showed that granules containing methanogens deep within them tended to float. Granules with a Bacteria layer on the surface also tended to float. On the basis of these findings, well-settled granules are considered to have methanogens that develop near the granule surface so that the gases generated during methane fermentation are readily released.