At the first meeting of the 52nd World Health Assembly in December 1999, two research objectives were identified as the primary reasons for retaining variola virus: the possible development of a more attenuated, less reactogenic smallpox vaccine and the possible development of an antiviral drug that could be used in treating patients with smallpox. This paper argues that these research objectives are not sufficiently important to warrant retaining any stocks of variola virus. In the United States, a vaccine strain that would be as effective as the New York Board of Health (NYBOH) strain but that would be less prone to induce complications was originally viewed as a desirable objective; however, existing vaccine strains (NYBOH and Lister, for example) have been shown in the circumstances of a natural challenge to provide solid protection to almost all who received them, even when administered 2-3 days after exposure. Additional NYBOH vaccine has been procured for the U.S. national reserve. This effectively forecloses the rationale for further research on modified vaccines. Further, it is more logical to focus research efforts on the development of an antivaccinial drug that could be used to treat cases of progressive vaccinia should they occur. Such a drug could be much more fully evaluated in animal studies, thus providing a high level of confidence that it would be effective when circumstances called for its use. Such research would not require retention of variola virus. There might be logic in a broad-based research program to explore the range of possible alterations in the genome that might be induced and so better define the nature of the threat; however, such experiments would not only be in direct violation of the Biologic and Toxin Weapons Convention, but they might define a whole new array of bioweapons. Thus, there is no justification for retaining stocks of variola virus for research, particularly given the increasing threat of bioterrorism. The World Health Assembly should call on each country to destroy its stocks of smallpox virus and state that any person, laboratory, or country found to have virus after a specified date would be guilty of a crime against humanity. 4 references