The high error rate inherent in all RNA synthesis provides RNA virus genomes with extremely high mutation rates. Thus nearly all large RNA virus clonal populations are quasispecies collections of differing, related genomes (14, 49). These rapidly mutating populations can remain remarkably stable under certain conditions of replication. Under other conditions, virus-population equilibria become disturbed, and extremely rapid evolution can result. This extreme variability and rapid evolution can cause severe problems with previously unknown virus diseases (such as AIDS). It also presents daunting challenges for the design of effective vaccines for the control of diseases caused by rapidly evolving RNA virus populations.