Brazilian spotted fever (BSf), caused by Rickettsia rickettsii, is the most lethal tick-borne disease in the western hemisphere. in Brazil, Amblyomma sculptum ticks are the main vector. capybaras (Hydrochoerus hydrochaeris), the largest living rodents of the world (adults weighing up to 100 Kg), have been recognized as amplifying hosts of R. rickettsii for A. sculptum in BSf-endemic areas; i.e., once primarily infected, capybaras develop bacteremia for a few days, when feeding ticks acquire rickettsial infection. We conducted experimental infections of five capybaras with an A. sculptum-derived strain of R. rickettsii and performed clinical and bacteremia evaluation during primary and subsequent infections. Bacteremia was detected in all capybaras during primary infection, but not in subsequent infections. All animals seroconverted to R. rickettsii (titres range: 64-32,768), and remained seropositive throughout the study. primary infection resulted in clinical spotted fever illness in four capybaras, of which two had a fatal outcome. Subsequent infections in seropositive capybaras resulted in no clinical signs. capybaras developed a sustained immune response that prevented a second bacteremia. this condition may imply a high reproduction rate of capybaras in BSf-endemic areas, in order to continuously generate capybaras susceptible to bacteremia during primary infection. The bacterium Rickettsia rickettsii is the etiological agent of Rocky Mountain spotted fever, also known in Brazil as Brazilian spotted fever (BSF), a disease that has been registered in different American countries including Canada, United States, Mexico, Costa Rica, Panama, Colombia and Argentina 1,2. This bacterium is transmitted by different tick species throughout Americas [i.e., Dermacentor variabilis, Dermacentor andersoni, Rhipicephalus sanguineus sensu lato (s.l.), Amblyomma cajennense species complex, and Amblyomma aureolatum] 2. In Brazil, in the southeastern region, Amblyomma sculptum (a member of A. cajennense species complex) is the main incriminated vector, for which capybaras (Hydrochoerus hydrochaeris) and horses act as primary hosts for all parasitic stages 3,4. BSF is the most lethal tick-borne disease in Brazil with increasing numbers of cases and deaths. Between 2007 and 2015, 17,117 suspected cases of spotted fever (including other spotted fever group rickettsioses) were reported and 1,245 were confirmed as SFG rickettsioses in 12 Brazilian states from all regions 1. Moreover, case-fatality rates have attained values of 30% or higher, which could be associated with low index of suspicion and misdiagnosis by health-care professionals and exposure to particular eco-epidemiological risk factors 1 .