This study describes the detection of cytokines, interleukin-1 alpha (IL-1 alpha), tumor necrosis-factor alpha (TNF alpha) and interleukin-6 (IL-6) in the serum and brain homogenates of susceptible and resistant strains of mice infected with distinct species/strains of Borrelia. Significant elevation of inflammatory cytokines was found in the sera of susceptible C3H/ HeN mice but not in the sera of resistant BALB/c mice on days 7 and 45 after inoculation. Brain cytokines were observed in C3H/HeN mice infected with B. garinii and B. afzelii and the production was associated with the presence of spirochetes. B. japonica was the only exception in disease-susceptibility and cytokine production of mice. These results suggest that there are differences in pathogenic potential amongst Borrelia strains, and that the susceptible mice demonstrate a stronger cytokine response and greater frequency of recovery of Borrelia from the brain than do the resistant mice.