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The indiscriminate use of acaricides has resulted in increasingly resistant populations, highlighting the need for alternative control strategies and pharmacological approaches, such as the use of synergists to enhance acaricide efficacy against resistant ticks. This study evaluated the effect of piperonyl butoxide (PBO) as a synergist in modulating resistance to ivermectin, eprinomectin, and moxidectin in five tick populations from the semi-arid area of Northeast Brazil. Bioassays revealed widespread resistance, with variation in LC50 values among locations, likely reflecting differences in the intensity and frequency of macrocyclic lactone use and, consequently, differences in resistance intensity rather than evidence of distinct resistance mechanisms. The association of PBO with macrocyclic lactones resulted in significant synergism in the studied tick populations. A notable reduction in LC50 was observed in 3 out of 5 populations for ivermectin, 4 out of 5 populations for eprinomectin, and 3 out of 5 populations for moxidectin. Even in highly resistant populations to moxidectin, a marked decrease in LC50 was observed after PBO exposure. These results indicate a pharmacological interaction between PBO and macrocyclic lactones, consistent with a partial contribution of oxidative detoxification to the resistance phenotype. However, the absence of synergism in some populations and the persistence of high resistance levels suggest that additional mechanisms are also involved.\n                  <\/jats:p>","DOI":"10.1007\/s10493-026-01164-5","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:26:08Z","timestamp":1784733968000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synergistic action of piperonyl butoxide with macrocyclic lactones in\u00a0Rhipicephalus microplus"],"prefix":"10.1007","volume":"97","author":[{"given":"Larissa Claudino","family":"Ferreira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Maria Santos","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordania Oliveira","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thais Ferreira","family":"Feitosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme Marcondes","family":"Klafke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vin\u00edcius Longo Ribeiro","family":"Vilela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"1164_CR1","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s10493-025-01011-z","volume":"94","author":"FBV Alvares","year":"2025","unstructured":"Alvares FBV, Ferreira LC, Silva JO, Lima AMS, Feitosa TF, Vilela VLR (2025) Acaricidal efficacy of the monoterpene linalool against the cattle tick Rhipicephalus microplus and its synergistic potential with cypermethrin. 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