The evolutionary suppression of synonymous codon sites is a controversial topic. Although some studies have indicated that synonymous substitution is under positive selection, most of these studies relied on comparison of homologous genes and/or a limited number of sequences. In the present work, we compared the selection strength at synonymous sites for two types of protein-encoding genes: genes encoding enzymes and protein genes encoding non-enzymes. Our method does not require assumptions concerning, for example, evolutionary equilibrium or population size. We compared ∼70 000 genes from the fully sequenced mammalian