Relative disease risk is strongly influenced by the ecological factors underlying disease transmission. Host species differ in their ability to act as a disease reservoir, and consequently, the relative abundance of different host species will affect levels of disease risk. Lyme disease, caused by Borrelia burgdorferi, is a tick-borne zoonotic disease that infects a broad range of hosts. Disease risk varies widely (e.g. 0.3 to 51.6 cases per 100,000 people in California and Connecticut, respectively in 2006). Using simple models and empirical data, we show that disease risk reflects host community ecology. In California, western gray squirrels (Sciurus griseus) are important reservoirs of the Lyme disease spirochete in oak woodlands. In contrast, fence lizards (Sceloporus occidentalis) host large numbers of ticks but actively destroy the disease agent. We demonstrate how the relative densities of these two hosts, combined with their disparate roles as Borrelia burgdorferi reservoirs, influence the density of infected nymphal ticks in California.