Although molecular evolution often appears to proceed in a clocklike fashion, examples to the contrary are increasing in number. Our study compares rate 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 substitution. Rate of nonsynonymous substitution differs significantly among many of the rodents studied. However, the cause or causes of these differences in substitution rate remains in question. Differences in generation time, body size, or metabolic rate do not seem to be associated with rate of nonsynonymous substitution in these rodents. Effective population size remains a viable explanation of the observed rate heterogeneity. However, we suggest that a search for simple causes of differences in rate of molecular evolution may be difficult in light of numerous aspects of an organism's biology that may together influence evolutionary rates over space and time.