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The nonsynonymous/synonymous rate ratio (ω = d_N/d_S) is an important measure of the mode and strength of natural selection acting on nonsynonymous mutations in protein-coding genes. The simplest such analysis is the estimation of the d_N/d_S ratio using two sequences. Both heuristic counting methods and the maximum-likelihood (ML) method based on a codon substitution model are widely used for such analysis. However, these methods do not have nice statistical properties, as the estimates can be zero or infinity in some data sets, so that their means and variances are infinite. In large genome-scale comparisons, such extreme estimates (either 0 or ∞) of ω and sequence distance (t) are common. Here, we implement a Bayesian method to estimate ω and t in pairwise sequence comparisons. Using a combination of computer simulation and real data analysis, we show that the Bayesian estimates have …