Mutation frequency decline is the rapid and irreversible decline in the suppressor mutation frequency of Escherichia coli cells if the cells are kept in nongrowth media immediately following the mutagenic treatment. The gene mfd, which is necessary for mutation frequency decline, encodes a protein of 130 kDa which couples transcription to excision repair by binding to RNA polymerase and to UvrA, which is the damage recognition subunit of the excision repair enzyme. Although current evidence suggests that transcription-repair coupling is the cause of the preferential repair of the transcribed strand of mRNA encoding genes as well as of suppressor tRNA genes, the decline occurs under stringent response conditions in which the tRNA genes are not efficiently transcribed. Thus, the mechanism of strand-specific repair is well understood, but some questions remain regarding the precise mechanism of mutation frequency decline.