The products of the Escherichia coli umuDC operon and its plasmid-borne analog, mucAB, are required for mutagenesis caused by UV light and by many chemicals. We have determined the nucleotide sequences of umuDC and mucAB and present comparisons of these sequences. The two operons are 52% homologous at the nucleotide level. Open reading frames corresponding in position and size to the umu and muc genes have been identified. The reading frames of umuD and umuC overlap by 1 base pair, and the reading frames of mucA and mucB overlap by 13 base pairs. The predicted amino acid sequences of the UmuD and MucA proteins are 41% homologous; those of the UmuC and MucB proteins are 55% homologous. Considerable homology has also been detected between UmuD, MucA, and the COOH-terminal domains of the LexA repressor and the repressors of phage lambda, 434, and P22. Complementation analyses reveal that MucA protein cannot substitute for UmuD in a umuD- umuC+ host and that MucB protein cannot substitute for UmuC in a umuD+ umuC- host. Potential regulatory sequences have been identified in umuDC and mucAB.