The quasispecies model of RNA virus evolution differs from those formulated in conventional population genetics in that neutral mutations do not lead to genetic drift of the population, and natural selection acts on the mutant distribution as a whole rather than on individual variants. By computer simulation, we show that this model could be inappropriate for many RNA viruses because the neutral sequence space may be too large to allow the formation of a quasispecies distribution. This view is supported by our analysis of gene sequences from vesicular stomatitis virus, which is considered a prototype RNA virus quasispecies. Our results are relevant to the evolution of RNA systems in general.