This investigation of the codon context of enterobacteria, plasmid, and phage protein genes was based on a search for correlations between the presence of one base type at codon position III and the presence of another base type at some other position in adjacent codons. Enterobacterial genes were compared with eukaryotic sequences for codon context effects. In enterobacterial genes, base usage at codon position III is correlated with the third position of the upstream adjacent codon and with all three positions of the downstream codon. Plasmid genes are free of context biases. Phage genes are heterogeneous: MS2 codons have no biased context, whereas lambda genes partly follow the trends of the host bacterium, and T7 genes have biased codon contexts that differ from those of the host. It has been reported that two successive third-codon positions tend to be occupied by two purines or two pyrim-idines in Escherichia coli genes of low expression level. Here, the extent to which highly expressed protein genes can modulate base usage at two successive codon positions III, given the constraints on codon usage and protein sequence that act on them, was quantified. This demonstrates that the above-mentioned favored patterns are not a characteristic of weakly expressed genes but occur in all genes in which codon context can vary appreciably. The correlation between successive third-codon positions is a distinct feature of enterobacteria and of some phages, one that may result from adaptation of gene structure to translational efficiency. Conversely, codon context in yeast and human genes is biased-but for reasons unrelated to translation.