DNAs were prepared from twenty-six bacterial species and digested with a variety of restriction endonucleases to determine what modifications the DNAs carry. Several general conclusions could be made: 1) First, in no instance was the DNA of a restriction enzyme. 2) The specificity of the DNA modification was the same as that of its restriction counterpart; there were no cases of the DNAs being modified against a less specific class of restriction enzymes. 3) In most (but not all) cases, the resistance of a bacterium's DNA to its own restriction enzyme could be generalized to include resistance to all other restriction enzymes with the same specificity (isoschizomers). 4) DNA modified within the central tetramer of a recognition sequence is usually protected against cleavage by all related hexameric enzymes possessing that central tetramer. Only three families of DNA presented in this study disobey this rule. 5) Finally, a significant number of cases emerge where bacterial DNA carries a modification but no corresponding restriction endonuclease activity.