We studied the influence of the codon context on UGA suppression by a suppressor tRNA and on UGA readthrough by a normal tRNA in Escherichia coli. This was done by a series of constructs where only the immediate context of the TGA codon was varied by only one nucleotide at a time. For both UGA suppression and UGA readthrough the codon context had a similar influence according to the following rules. (1) The nature of the nucleotide immediately adjacent to the 3' side of the UGA is an important determinant; at that position the level of UGA translation is influenced by the nucleotides in the order A greater than G greater than C greater than U. (2) At extremely high or low levels of UGA translation this influence of the adjacent 3' nucleotide is not seen. (3) In all cases, the nature of both the nucleotide immediately adjacent to the 5' side of the codon and that following the base adjacent to the 3' side of the codon have little effect, if any, on UGA translation. The varying influence of the codon context effect on UGA translation is discussed in relation to its role in gene expression.