Background: Arenaviruses are negative strand RNA viruses that can cause disease and hemorrhagic fever in humans. Flexal virus (FLEV) is a New World arenavirus that was isolated in Brazil from the Oryzomys ssp. (Rice rat). This virus is classified as a HHS and USDA Select Agent and is known to be a human pathogen that has caused mortality in humans. Currently, there has not been a description of an animal model to study FLEV induced pathogenesis. Therefore, this study aimed to characterize an animal model to study FLEV pathogenesis.Methods and Findings: In this study, we infected hamsters 5-6 weeks of age and 13-15 weeks of age) and guinea pigs with FLEV. The results demonstrate that there are discernable differences associated with FLEV infection in these 3 animal models. FLEV infection in 5-6 week old Syrian golden hamsters resulted in 60% mortality, while infection in the 13-15 week old hamsters resulted in 80% mortality. Infection in guinea pigs resulted in only 20% mortality. FLEV infection in hamsters resulted in hemorrhagic fever manifestations, which included morbidity, weight loss, petechial rash, and hemorrhage. Additionally, FLEV was isolated in specific tissues from the terminal hamsters and viremia was measured in terminal samples. Vascular leakage was associated with the lung, spleen, intestines, brain, heart, kidney, and pancreas in terminal hamsters. Lastly, mortality appeared to correlate with viral tissue titers and viremia.Conclusions: In all, this study demonstrates that the Syrian golden hamster serves as an appropriate animal model to study FLEV-induced pathology and vaccine and therapeutic efficacy