Escherichia coli CcmA, CcmB and CcmC polypeptides are required for cytochrome c synthesis and are thought to constitute the subunits of an ABC-type transporter as judged from sequence data. Using a periplasmic reporter system based on Bacillus subtilis cytochrome c-550 and E. coli cytochrome b-562 we show that the synthesis of the b-type cytochrome in the periplasm is normal in E. coli ccmA and ccmC in-frame deletion mutants. Mutants deleted for ccmF or ccmG encoding a component of a putative cytochrome c-heme lyase and a membrane bound thioredoxin-like protein, respectively, have the same phenotype. The ccm mutants produce cytochrome c-550 polypeptide, but not holocytochrome c. Taken together the results demonstrate that heme can be transported to the periplasm by a ccm-independent mechanism.