In the host-controlled modification of phage λ by fi- R factors, N-3 and R-15, the infectivity of the unmodified λ DNA was specifically destroyed by the sonicated extracts from the restrictive, endonuclease I-less (endo I-less) mutant of Escherichia coli K12 carrying N-3 or R-15, to a greater extent than by the sonicates from the nonrestrictive, endo I-less bacteria. In the control experiments, the λ DNA modified by N-3 was inactivated to much lesser extents both by the sonicates from the restrictive, endo I-less bacteria and by those from the nonrestrictive, endo I-less bacteria. In all these systems of reactions, the phage DNA was hardly degraded into acid-soluble forms. The host specifically inactivated, unmodified λ DNA, however, was split fragmentally as was shown by the patterns of zone sedimentation, but the modified λ DNA was not. The activity which destroys the infectivity of the unmodified λ DNA resided totally in the spheroplasts of the restrictive bacteria. © 1968.