Type II restriction modification systems (RMSs) have been regarded either as defense tools or as molecular parasites of bacteria. We extensively analyzed their evolutionary role from the study of their impact in the complete genomes of 26 bacteria and 35 phages in terms of palindrome avoidance. This analysis reveals that palindrome avoidance is not universally spread among bacterial species and that it does not correlate with taxonomic proximity. Palindrome avoidance is also not universal among bacteriophage, even when their hosts code for RMSs, and depends strongly on the genetic material of the phage. Interestingly, palindrome avoidance is intimately correlated with the infective behavior of the phage. We observe that the degree of palindrome and restriction site avoidance is significantly and consistently less important in phages than in their bacterial hosts. This result brings to the fore a larger selective load for palindrome and restriction site avoidance on the bacterial hosts than on their infecting phages. It is then consistent with a view where type II RMSs are considered as parasites possibly at the verge of mutualism. As a consequence, RMSs constitute a nontrivial third player in the host-parasite relationship between bacteria and phages.Classic type II restriction modification systems (RMSs) comprise pairs of enzymes with matching DNA sequence specificity. The modification enzyme is a DNA methyltransferase that specifically methylates either adenosyl or cytosyl residues within the recognition sequence (the restriction site; RS), thus making DNA resistant to the restriction activity. The restriction enzyme is an endodeoxyribonuclease that cleaves DNA at a precise location within or around the recognition sequence, when this sequence is not methylated (Redaschi and Bickle 1996). These recognition sequences are symmetrical, comprising 4-8 specific base pairs, and cleavage and methylation occur symmetrically within the sequences. As a consequence, foreign double stranded DNA (dsDNA), unmethylated at the restriction sites recognized by the cell's RMS, is quickly degraded.