Cattle exposed to a paralyzing strain of Dermacentor andersoni (Stiles) were all paralyzed during an initial exposure, but the incidence of paralysis decreased to 17 and 0% after two subsequent exposures to virulent flat ticks. Cattle with a single exposure to paralyzing ticks became paralyzed when challenged with ticks that had been prefed on cattle. Western blots indicated that cattle developed antibody responses to 13 antigens in paralyzing tick saliva. The likelihood of paralysis was inversely related to the number of saliva proteins that cattle developed antibody responses to. Cattle challenged with prefed ticks developed antibody response to fewer saliva antigens than cattle challenged with flat ticks. Variation in tick dose did not influence the expression of paralysis. Daily survival of ticks was similar on all groups of cattle, and tick weight was not reduced on previously challenged cattle, indicating immunity developed to the paralysis toxin rather than tick feeding. Four saliva antigens (molecular weights ranging from 36.9 to 42.2 kDa) were associated with the development of immunity to paralysis.