The acquisition of resistance in goats against Amblyomma cajennense after repeated infestations and the role of inflammatory cells in this mechanism were investigated. Ten naive goats aged 6 months were distributed into two groups: test (n= 5), infested thrice at 30‐day intervals; and control (n= 5), infested once. Nymphs (n= 115 per animal per infestation) were released inside alimentary chambers glued to the animal's dorsum and the following biological parameters were evaluated: yielding rate, nymphal engorgement weight, engorgement period, ecdise rate, and ecdise period. Skin fragments of tick bite sites were collected at 24, 48, 72, and 120 h post attachment for histopathology and inflammatory cells counts. The engorgement weight decreased significantly (P < 0.05) from the first infestation onward; nymphs weighed 41.7% and 37.1% less after the second and third infestations, respectively, as compared to those collected after the first infestation (12.55 mg ± 3.21). Furthermore, the ecdise period increased significantly (P < 0.05) in the third infestation (18 days ± 2.83) in comparison with the first infestation (15 days ± 0.82) and the ecdise rate was significantly lower after the second infestation (71.91%± 17.38) in comparison with the first infestation (96.89%± 3.38). There were no significant differences with regard to both the engorgement period and yielding rate. A cutaneous basophilia was evidenced between 48 and 72 h (P < 0.05) after both the second and third infestations. We conclude that goats develop resistance against nymphs of A. cajennense and that basophils may play an important role in such a mechanism.