Several models have been proposed to account for the segmentation of RNA vi
ruses. One of the best known models suggests that segmentation, and mixing
of segments during coinfections, is a way to eliminate deleterious mutation
s from the genome. However, for validity, this model requires that deleteri
ous mutations interact in a synergistic way. That is, two mutations togethe
r should have a more deleterious effect than the result of adding their ind
ividual effects. Here I present evidence that deleterious mutations in foot
-and-mouth disease virus produce a decline in fitness but that the relation
ship between the number of mutations fixed and the magnitude of fitness dec
line is compatible mainly with a nonsynergistic model. However, the statist
ical uncertainties associated with the data still give some room for the ex
istence of very weak synergistic epistasis.