Lassa virus (LASV) is the causative agent of Lassa hemorrhagic fever (LF) in humans, a deadly disease endemic toWest Africa that results in 5,000 to 10,000 deaths annually. Here we present results demonstrating that functional type I and type II inter-feron (IFN) signaling is required for efficient control of LASV dissemination and clearance. Lassa virus (LASV), an arenavirus (family Arenaviridae), isenveloped and contains two single-stranded RNA segments of ambisense polarity encoding five proteins (1). LASV is the etiological agent of Lassa hemorrhagic fever (LF), a severe hu-man disease that is reported in up to 100,000 patients annually in regions where it is endemic. Mortality varies between 5% and 10 % for hospitalized patients (3). I...