A., T. countries within Asia and to Europe and North America in early 2003. The syndrome is characterized by fever, chills or rigors, headache, and nonspecific symptoms such as malaise and myalgias, followed by cough and dyspnea (2, 5, 15). According to the World Health Organization, 8,437 cases of SARS had been identified worldwide as of 11 July 2003 and 813 patients had died, resulting in an overall mortality rate of 9.6% (World Health Organization, http://www.who.int/csr/sars/country/2003_07_11). Respiratory tract disease progresses to acute respiratory distress syndrome, requiring intensive care and mechanical ventilation for more than 20% of patients (9, 15, 16). Prolonged hospitalizations associated with complications have been reported (9, 15). Public health measures, including early admission, contact tracing, quarantine, and travel restrictions, were instituted to control the spread of the disease (5), and the World Health Organization declared that the outbreak was over in July 2003. The severe morbidity and mortality associated with SARS make it imperative that effective means to prevent and treat the disease be developed and evaluated, especially since it is not known whether the virus will reappear and exhibit a seasonal pattern of circulation like other respiratory virus pathogens or whether it will be independently reintroduced into the human population. Prevention and treatment strategies can be developed based on principles that apply to other pathogens, but evaluation of the efficacy of these strategies requires animal models. Coronaviruses are generally restricted in their host range, and viruses associated with disease in one species can be limited in their ability to replicate in other species (reviewed in reference 12). SARS-CoV differs from this general pattern because it is likely an animal virus that infects humans. Although closely related viruses Chimaphilin have been isolated from animal species in southern China, it is not clear which animal species represents the reservoir from which the virus entered the human population (11). Cynomolgus macaques have been reported to develop pathological findings of pneumonia and have been proposed as an animal model for SARS (14). However, small-animal models, such as rodents, would be very useful for evaluating vaccines, immunotherapies, and antiviral drugs, and we have identified the mouse as a useful animal model for this purpose. MATERIALS AND METHODS Virus and cells. L. J. Anderson and T. G. Ksiazek from the Centers for Disease Control and Prevention (CDC), Atlanta, Ga., kindly provided the SARS-CoV (Urbani strain) used in this study (13). The virus was isolated and passaged twice in Vero E6 cells at the CDC and was passaged in Vero cells for two additional passages in our laboratory to generate a virus stock with a titer of 106.5 50% tissue culture infective doses (TCID50)/ml. The Vero cells were maintained in OptiPro Chimaphilin SFM Chimaphilin (Invitrogen, Carlsbad, Calif.). All work with infectious virus was performed inside a biosafety cabinet, in a biosafety containment level 3 facility, and personnel wore powered air-purifying respirators (HEPA AirMate; 3M, Saint Paul, Minn.). Animal studies. Mst1 The mouse studies were approved by the National Institutes of Health Animal Care and Use Committee and were carried out in an approved animal biosafety level 3 facility. All personnel entering the facility wore powered air purifying respirators (HEPA AirMate). Female BALB/c mice 4 to 6 6 weeks old purchased from Taconic (Germantown, N.Y.) were housed four per cage. Mice that were lightly anesthetized with isoflurane were inoculated with 50 l of diluted virus intranasally. On days 1, 2, 3, 5, 7, 9, and 11, mice were euthanized with carbon dioxide, and the lungs, nasal turbinates, and spleen were removed and stored at ?70C until the end of the study. In a separate experiment, mice were euthanized 2 days following virus administration, and the liver, kidneys, and part of the small intestine were removed and stored at ?70C. The frozen tissues were thawed and homogenized in a.