Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus termed SARS-CoV. No antiviral treatment has been established so far. Interferons are cytokines which induce the synthesis of several antivirally active proteins in the cell. In this study, we demonstrated that multiplication of SARS-CoV in cell culture can be strongly inhibited by pretreatment with interferon-beta. Interferon-alpha and interferon-gamma, by contrast, were less effective. The human MxA protein is one of the most prominent proteins induced by interferon-beta. Nevertheless, no interference with SARS-CoV replication was observed in Vero cells stably expressing MxA. Therefore, other interferon-induced proteins must be responsible for the strong inhibitory effect of interferon-beta against SARS-CoV.