Background: The type 1 interferons (INF-α and INF-β) are potent antiviral agents. Albumin-INF-α and albumin-INF-β are novel recombinant proteins consisting of IFN-α or IFN-β genetically fused to human albumin. Methods: The in vitro antiviral activity of albumin-IFN-α was evaluated against representative bioterrorism viral agents and the severe acute respiratory syndrome virus. Antiviral activity was assessed using inhibition of cytopathic effect and neutral red staining. Results: EC50 values for albumin-IFN-α ranged fromConclusion: Further evaluation of these long-acting albumin-IFN fusion proteins as prophylactic or therapeutic agents against these viral agents of bioterrorism in relevant primate models is warranted.