Multimer formation and consequent copy number depression are acknowledged causes of multicopy plasmid instability. Multimer resolution sites (among which ColE1 cer is best-characterized) have been identified in a variety of plasmids. They participate in the conversion of multimers to monomers, maximizing the number of independently segregating molecules and minimizing the frequency of plasmid loss. We show that multimer resolution alone is insufficient to ensure stable maintenance of ColE1-like plasmids in a recombination-proficient host. The expression of Red, a transcript encoded within cer and expressed in multimer-containing cells, is also required. The appearance of Red correlates with the inhibition of division of multimer-containing cells, presumably allowing time for the conversion of multimers to monomers by site-specific recombination.