Four North American and two European species of Ixodes ticks harbor borreliae. Three of the North American species — Ixodes dammini, Ixodes scapularis, and Ixodes pacificus — and two Old World species — Ixodes ricinus and Ixodes persulcatus — feed on a wide range of hosts, including humans; the North American Ixodes dentatus has a predilection for cottontail rabbits and rarely parasitizes humans. In Lyme disease foci in North America where I. dammini is common, Borrelia burgdorferi or similar types of spirochetes havebeen cultured from 10 species of wild or domestic mammals and from one species of songbird. The prevalence of infected rodents is remarkably high (≥75%) in these foci. Several different antigenic variants of B. burgdorferi have been cultured. Initial isolates of B. burgdorferi in North America were remarkably homogeneous, but documentation of different variants is increasing. The association of different antigenic variants with diseases in humans and domestic animals needs to be clarified.