Campylobacter jejuni is naturally transformable but is selective in the DNA used in transformation. Natural transformation allows for rapid adaptation and provides a means for DNA repair, both of which enhance bacterial fitness. Our work demonstrates that the methylation status of C. jejuni DNA is critical for transformation; methylation of a single 6-bp sequence in proximity to the transforming DNA is sufficient to allow nontransforming DNA to transform C. jejuni. Our data argue against previously described means for DNA discrimination; specifically, there is no evidence that a restriction enzyme recognizes the unmodified 6-bp sequence, and no evidence of a typical DNA uptake sequence. Therefore, we have identified a distinct DNA discrimination mechanism in Campylobacter