Viral hemorrhagic fevers, because of their high mortality rates, the lack of medical countermeasures, and their potential use as instruments of bioterrorism, pose a significant threat to the developed and the developing areas of the world. The key to preventing the spread of these diseases is early and accurate detection. For decades, the gold-standard immunoassay for hemorrhagic fever detection has been the enzyme-linked immunosorbent assay (ELISA); however, newer technologies are emerging with increased sensitivities. One such technology is the Luminex MagPix platform using xMAP microspheres. Here, we compare the MagPix platform with a traditional ELISA for IgM and antigen detection of infections from Lassa and Ebola viruses (LASV and EBOV, respectively). For IgM detection in nonhuman primate samples, the MagPix platform was 5 and 25 times more sensitive in detecting LASV and EBOV, respectively, compared to that with ELISA. For antigen detection in buffer, the MagPix platform was 25 and 2.5 times more sensitive in detecting lower levels of LASV and EBOV, respectively. In both IgM and antigen detection assays, the MagPix platform demonstrated excellent reproducibility at the lower limit of detection (LLOD). These findings demonstrate that the MagPix platform is a viable diagnostic replacement for the ELISA for viral hemorrhagic fevers.KEYWORDS ELISA, MagPix, Ebola virus, immunoassays, Lassa virus, viral hemorrhagic fever H emorrhagic fevers are a part of the normal disease burden in Africa. In the developed world, they are a concern because of their potential use as bioterrorism agents. Lassa virus (family, Arenaviridae) and ebolaviruses (family, Filoviridae) are hemorrhagic fever viruses that are endemic in several African countries (1, 2). Disease outbreaks with these viruses have significant medical and social impacts. Case fatality rates can be as high as 65% for Lassa virus (LASV) and as high as 90% for ebolaviruses (3,4). Their high mortality rates combined with their ease of transmission and the lack of vaccines or effective treatments render them extremely dangerous pathogens.Early during an infection, hemorrhagic fever viruses have a clinical presentation that is similar to other more common febrile illnesses (5, 6). A rapid and accurate diagnosis of hemorrhagic fever viruses is critical for limiting the spread of disease and enabling an earlier more effective treatment. Traditionally, enzyme-linked immunosorbent assays (ELISAs) have been used for the detection of a virus-specific antigen and/or IgM antibodies (7,8).ELISA immunodiagnostics are the standard by which other diagnostics are evaluated. ELISA has been commonly used for the detection of LASV and Ebola virus (EBOV) for many years; however, newer immunodiagnostic platforms that offer multiplex