AbstractAndes virus (ANDV) is responsible for the Hantavirus Pulmonary Syndrome cases in Argentina and neighboring countries, with moderate to high case‐fatality rates. ANDV has some particular features, which make it unique among other members of the Hantavirus genus such as person‐to‐person transmission and causing a disease similar to Hantavirus Pulmonary Syndrome in the hamster as an animal model. The kinetics of replication in Vero E6 cells of an ANDV strain isolated in Argentina, called Andes/ARG, was studied. Cytopathic effect and the formation of clear plaques were observed and therefore Andes/ARG could be quantified by classic plaque assay. The Andes/ARG strain was found to be highly lethal in Syrian hamsters allowing experiments to demonstrate the protective potential of vaccines. A recombinant nucleocapsid protein of ANDV induced a long lasting antibody response and protective immunity against a homologous challenge, but to a lower extent against heterologous challenge by the Seoul virus. J. Med. Virol. 84:87–95, 2011. © 2011 Wiley Periodicals, Inc.