Attempts to infect juvenile and adult western fence lizards (Sceloporus occidentalis) with the Lyme borreliosis spirochete (Borrelia burgdorferi) were largely unsuccessful. Spirochetes could not be isolated from the blood and various tissues of 14 lizards 21-32 days after they had been inoculated ip (n = 8) or sc (n = 6) with 10(6) or 10(8) B. burgdorferi representing 3 tick isolates, although 1 lizard apparently developed a transitory spirochetemia lasting 2 days. Similarly, spirochetes could not be detected in the blood or tissues of 5 lizards fed upon by 2- greater than 8 infected larvae or nymphs of the western black-legged tick (Ixodes pacificus). Sixty-five blood samples from 59 lizards in an endemic area and various tissues from 20 of the same lizards were also assayed for B. burgdorferi with negative results. The implications of these findings for the maintenance of this spirochete in natural foci are discussed.