Type II restriction-modification gene complexes, such as the EcoRI system, are not easily lost from their host cell. The descendants of cells that lose a restriction-modification gene complex are unable to modify a sufficient number of recognition sites in their chromosomes to protect them from lethal attack by the remaining molecules of restriction enzyme. This capacity to act as a selfish genetic element is likely to have contributed to the spread and maintenance of restriction-modification systems. Homologous recombination machineries of cells and viruses appear to be well adapted to cope with these elements. By extrapolation, the capacity of mitochondria to kill their host eukaryotic cell might have stabilized their initial symbiosis.