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The bacterium Yersinia pestis causes bubonic plague. In Central Asia, where human plague is still reported regularly, the bacterium is common in natural populations of great gerbils. By using field data from 1949–1995 and previously undescribed statistical techniques, we show that Y. pestis prevalence in gerbils increases with warmer springs and wetter summers: A 1°C increase in spring is predicted to lead to a >50% increase in prevalence. Climatic conditions favoring plague apparently existed in this region at the onset of the Black Death as well as when the most recent plague pandemic arose in the same region, and they are expected to continue or become more favorable as a result of climate change. Threats of outbreaks may thus be increasing where humans live in close contact with rodents and fleas (or other wildlife) harboring endemic plague.