Lyme disease is one of the most frequently reported infectious diseases in the United States. The bacteria that cause Lyme disease are transmitted by ticks to people, causing serious illness. The goal of this project is to synthesize 35 years of research to address both scientific theory of infectious diseases and to improve prediction and management of this disease. Lyme disease has become a model for understanding emerging diseases in the USA and worldwide. However, Lyme disease is a complex illness that involves interactions between ticks, bacteria, wildlife, forests, weather, suburbia, and people. Preventing this and related diseases requires improved understanding of where and when people are at greatest risk. Many ticks are infected with several pathogens, increasing human exposure to other infectious diseases. This project advances NSF’s priorities in biotechnology by providing a framework for decision making on modeling, prevention, and management of a complex and critical disease impacting human health and wildlife. A 35-year study of Lyme disease ecology has revealed surprising results inconsistent either with population theory and with expectations from shorter-term studies. For example, (1) despite deer being considered the main reproductive host for blacklegged ticks, long-term data show no effect of deer on densities of ticks, whereas the effect of rodents is considerably stronger. (2) Although white-footed mice are the most efficient host in transmitting zo