Protein A from Staphylococcus aureus is a powerful diagnostic reagent and has several uses in human disease therapy. Expression in non-pathogenic Escherichia coli containing recombinant plasmids coding for this protein has increased its availability, but can reduce the stability of the plasmid-bearing host. By employing immune electron microscopy, we have determined that E. coli containing stable plasmids coding for a truncated version of protein A, without the membrane binding site, secrete this protein through the cytoplasmic membrane and into the periplasmic space, where it accumulates. E. coli containing unstable plasmids, however, which code for the complete protein including the membrane-binding site, target the protein into the cytoplasmic membrane. This accumulation of protein A in the E. coli cytoplasmic membrane inhibits the formation of septa between dividing cells and results in aberrant elongated, multi-chromosomal forms.