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Plague and hantavirus pulmonary syndrome (HPS) are severe, often fatal diseases in humans that share a broad epidemiologic focus in the southwestern United States. Prevention of these diseases relies heavily on education and reducing rodent abundance in peridomestic environments. Resources for these activities are limited. Therefore, identifying areas sharing elevated risk for these two relatively rare but severe diseases could be useful for targeting limited public health resources. Using logistic regression and geographic information system–based modeling, we identified environmental predictors of elevated risk for plague (distance to piñon-juniper ecotones and amount of precipitation) and HPS (elevation and amount of precipitation) in northeastern Arizona and northwestern New Mexico. Our models accurately identified case locations as suitable (producer accuracies of 93% for plague and 96% for HPS) and indicated that approximately half of the coverage area was classified as suitable risk for either plague or HPS. The probability of a site being classified as suitable for plague was strongly correlated with its probability of being classified as suitable for HPS (ρs = 0.88). Increased risk for both diseases occurred for approximately 37% of the coverage area.