Although molecular evolution often appears to proceed in a clocklike fashio
n, examples to the contrary are increasing in number. Our study compares ra
te of cytochrome-b evolution in 21 rodent species, each of which belongs to
a different genus. In these comparisons, substitutions at synonymous sites
appear to be saturated, precluding inferences about rate of synonymous sub
stitution. Rate of nonsynonymous substitution differs significantly among m
any of the rodents studied. However, the cause or causes of these differenc
es in substitution rate remains in question. Differences in generation time
, body size, or metabolic rate do not seem to be associated with rate of no
nsynonymous substitution in these rodents. Effective population size remain
s a viable explanation of the observed rate heterogeneity. However, we sugg
est that a search for simple causes of differences in rate of molecular evo
lution may be difficult in light of numerous aspects of an organism's biolo
gy that may together influence evolutionary rates over space and time.