The present invention relates to improved compositions for the prevention and treatment of smallpox, and in particular to the use of compositions containing an antibody that binds to an epitope found on the MV form of the smallpox virus and an antibody that binds to an epitope found on the EV form of the smallpox virus. The invention relates to such compositions, especially to non-blood derived antibody compositions, such as chimeric or humanized antibodies, and to methods for their use in imparting passive immunity against smallpox infection to individuals at risk of smallpox virus infection or who exhibit smallpox.