Genetically mast cell-deficient (WB x C57BL/6)F₁-W/W^v mice show a defect in manifestation of resistance against larval Haemaphysalis longicornis ticks. In order to obtain direct evidence for anti-tick roles of mast cells, we examined whether intracutaneous injection of cultured mast cells normalized the defect of W/W^v mice. Bone marrow cells of (WB x C57BL/6)F₁-+/+ mice were cultured in the presence of pokeweed mitogen-stimulated spleen cell-conditioned medium. More than 95% of the cultured cells were identified as immature mast cells 4 wk after the initiation of the culture; the cells were harvested and directly injected into the skin of W/W^v mice. Mast cells appeared at the injection sites, where the resistance against the ticks was observed. Thus, mast cells developing at the injection sites seem to play an essential role for manifestation of resistance.