Infestation of larval Haemaphysalis longicornis ticks induced a threefold increase of eosinophils in the peripheral blood of normal WBB6F1-+/+ mice 2 days after tick infestation. In genetically mast cell-deficient WBB6F1-W/Wv mice, a threefold increase of blood eosinophils was observed 6 days after the tick infestation. However, marked infiltration of eosinophils was detected in the tick infestation sites of the WBB6F1-+/+ mice but not the WBB6F1-W/Wv mice. When the mast cell deficiency of WBB6F1-W/Wv mice had been rescued locally by intradermal injections of WBB6F1-+/+ mouse-derived cultured mast cells, a rapid increase of blood eosinophils and tissue infiltration of eosinophils were revealed following tick infestation. The intravenous (iv) injection of immune spleen or lymph node cells obtained from WBB6F1-+/+ mice 10 days after tick infestation led to significant eosinophilia in naive recipient mice. Treatment with anti-Thy-1.2 or anti-CD4 monoclonal antibody (mAb) and complement (C) completely abolished the eosinophilia; the early response (2 days after tick challenge) is dependent on mast cells at the feeding site, and the late response (6 days after tick challenge) is dependent on T lymphocytes. Since amplified interleukin-5 (IL-5) cDNA was detectable in the spleen cells 4 days after tick infestation, the late response might be mediated by IL-5. The infiltration of eosinophils at the feeding site of skin appeared to be dependent on mast cells.