Genetically mast cell-deficient (WB x C57BL/6)F_1^-W/W_v mice were used to investigate the role of mast cells for the acquisition of resistance against larval Haemaphysalis longicornis ticks. Resistance against ticks was evaluated by reduction in both number and weight of engorged ticks. Although (WB x C57BL/6)F_1^-+/+ mice with a normal number of mast cells acquired resistance after repeated infestation of ticks, the congenic W/W^v mice did not acquire it. Bone marrow transplantation from the +/+ mice rescued the mast cell depletion of the W/W^v mice; the rescued 443-6 mice did manifest resistance. When skin pieces of the +/+ mice were grafted onto the back of the W/W^v mice, resistance against the ticks was detectable in the grafted skin. In contrast, resistance was not detectable in the skin of the W/W^v mice which had been grafted onto the back of the syngenic W/W^v mice. Thus, we consider that the failure of the W/W^v mice to manifest resistance is attributable to the mast cell depletion.