The question of whether the known immunosuppressive effects of Babesia microti may disrupt the development of acquired resistance to its tick vector, Ixodes trianguliceps, in natural rodent hosts (Clethrionomys glareolus), and thus enhance the disease transmission potential, is addressed experimentally. The results show for the first time that natural hosts can acquire resistance to ticks; that this acquired resistance is manifested chiefly by a strongly density-dependent reduction in the percentage of attached larvae that engorge; that the density dependence is quantitatively similar whether the host receives occasional large tick challenges or frequent low infestations; but that infection with B. microti does not disrupt this pattern of acquired resistance. Of two important natural host species, Apodemus sylvaticus can support repeated infestations of I. trianguliceps, but is a poor host to B. microti, while C. glareolus develops acquired resistance to the tick vector, but supports much higher-level, longer-lasting B. microti infections.