Perhaps the most important factor to limit the effectiveness of vaccines against virus infections is that of virus variation. Successful vaccines have been developed against viruses such as those causing smallpox, measles, yellow fever and poliomyelitis, and they are effective against most circulating virus strains. However, with some viruses vaccination has been much less successful either because numerous antigenically distinct strains co-circulate, as is the case for rhinoviruses, or because new strains are continually emerging, as in the case of influenza virus. Despite the importance of virus variability, little is known about the factors that influence it and that are responsible for the dramatically different patterns of variation displayed by different viruses. The primary source of variation is obviously mutation, and it has been suggested in several recent papers that the extreme variability of some viruses may be a consequence of an unusually high rate of mutation (Holland et al., 1982; Reanney, 1984; Domingo et al., 1985; Saitou & Nei, 1986).