Lambda red gam phage carrying a 571 base-pair palindrome are unviable in wild-type Escherichia coli hosts. By using de-methylation to study the fate of DNA strands introduced into E. coli, we have demonstrated that a decrease in the yield of palindrome-containing molecules with two newly synthesized strands can occur without any concomitant loss of replicated molecules containing input strands. This implies that the palindrome-containing DNA is not being destroyed even as a consequence of replication, but rather that its replication rate is reduced. These results demonstrate that a palindrome can mediate unviability without directing cleavage of its carrier replicon.