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In general, rapid morphological change in mammals has been infrequently documented. Examples that do exist are almost exclusively of rodents on islands. Such changes are usually attributed to selective release or founder events related to restricted gene flow in island settings. Here we document rapid morphological changes in rodents in 20 of 28 museum series collected on four continents, including 15 of 23 mainland sites. Approximately 17,000 measurements were taken of 1302 rodents. Trends included both increases and decreases in the 15 morphological traits measured, but slightly more trends were towards larger size. Generalized linear models indicated that changes in several of the individual morphological traits were associated with changes in human population density, current temperature gradients, and/or trends in temperature and precipitation. When we restricted these analyses to samples taken in the US (where data on human population trends were presumed to be more accurate), we found changes in two additional traits to be positively correlated with changes in human population density. Principle component analysis revealed general trends in cranial and external size, but these general trends were uncorrelated with climate or human population density. Our results indicate that over the last 100+ years, rapid morphological change in rodents has occurred quite frequently, and that these changes have taken place on the mainland as well as on islands. Our results also suggest that these changes may be driven, at least in part, by human population growth and climate change.