The rapidity with which smallpox would spread in a developed nation is not known and is a major source of uncertainty in models used for public health planning (Ferguson et al., 2003) . The basic reproductive number (R 0 ), which describes the tendency of a disease to spread, has been estimated for smallpox from historical data and outbreaks in developing countries (Gani and Leach, 2001; Eichner and Dietz, 2003) . Because R 0 is a function of the contact rate between individuals, it can be affected by changes in the environment (Anderson and May, 1991) . A potentially important difference between contemporary environments and those used to estimate R 0 is that today many buildings, including hospitals, mechanically recirculate air. If smallpox was almost entirely transmitted by mucosal contact with large droplets (aerodynamic diameters >10 µm), which can only occur following "face-toface" exposure over distances of a few feet, then change in the built environment would not change the contact rate between individuals. If, however, smallpox was frequently transmitted from person-to-person by airborne droplet nuclei [fine particles with aerodynamic diameters of ≤2.5 µm capable of remaining suspended in air for hours and of depositing in the lower lung (Hinds, 1999) ] then mechanically recirculated air systems would increase the contact rate, R 0 , the risk of epidemic spread, and the difficulty of hospital infection control. Unfortunately, leading authorities disagree regarding the relative importance of fine and large particle routes of transmission; some state that smallpox was transmitted primarily via airborne droplet nuclei, (Henderson et al., 1999) while others emphasize "face-to-face" contact and state that, airborne transmission was rare (Centers for Disease Control, 2002; Mack, 2003) . This paper reviews the evidence for each of these modes of transmission.