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This study proposes a working hypothesis that Mediterranean hippopotamuses, and perhaps European ones as well, reduced their size, sometimes even drastically, from the ‘Mid-Pleistocene Revolution’ (MPR, c.1.2–0.5 Ma) to the Late Pleistocene. In contrast to the Early Pleistocene, during this time period glacial/interglacial cycling was dominated by a 100-ka periodicity, with more extended glacial phases (up to 85 ka) alternating with shorter interglacial phases (up to 15 ka). These changes seem to have somehow affected the size of hippopotamuses. While relatively larger hippopotamuses have been found in warmer and somewhat more humid intervals, data seem to indicate that they might not have grown as large under less favourable conditions, namely during colder and comparatively drier times. This is a possible response to climate-driven fluctuations in food availability, but Pleistocene habitat fragmentation may also have had an influence. Environmental break-up during the late Quaternary led to the isolation of megafauna populations, which underwent modifications similar to those observed in insular mammals. Although the amount of remains available is still limited, it is nonetheless a fact that hippopotamuses changed their body size through time, normally becoming smaller. If the conclusions are confirmed as data continue to accumulate, hippopotamuses might cast doubt on the generality of Bergmann's rule.