Tetracycline-resistant strains ofStaphylococcus aureus are minocycline sensitive, with the exception of strains susceptible to phages ofthe 83A/84/85 complex and some methicillin-resistant strains of other phage types. Strains of the 83A/ 84/85 complex yield mutants with increased mimocycline resistance. Transduction of minocycline resistance into the susceptible strain RN 450 was obtained with donor strains possessing either markers for both extrachromosomal tetracycline resistance (tet) and chromosomal tetracycline + minocycline resistance (tmn R), or only for chromosomal tmn R resistance. The chromosomal marker was differentiated from the extrachromosomal marker by the lack of detectable extrachromosomal deoxyribonucleic acid after transfer into strain RN 450, transfer into a rec+ strain, lack of transfer into rec-acceptor strain, and cotransduction with chromosomal determinants for guanine biosynthesis. Both chromosomal and extrachromosomal tetracycline resistance can be induced by tetracycline. Induction by tetracycline of chromosomal tetracycline resistance resulted in simultaneous induction of minocycline resistance. The mutation toward increased minocycline resistance (tmn -) tmn R) is a regulatory mutation toward constitutivity or semiconstitutivity. Constitutive resistance is dominant in tmn R/tet diploids. Transfer of the tet marker does not affect the phage susceptibility of the acceptor strain. The tmn R marker, originating from donor strains of the 83A/84/85 complex, renders strain RN 450 resistant to several typing phages, with the exception ofphages ofthe 83A/84/85 complex. This could possibly account for the phage typing patterns ofminocycline-resistant staphylococci.In most instances tetracycline resistance in Staphylococcus aureus and gram-negative bacteria is extrachromosomal (21, 25). Chromosomal resistance has been reported for a methicillin-resistant strain of S. aureus (15) and Escherichia coli (8). The mechanism oftetracycline resistance in S. aureus and E. coli is still not fully understood. A decrease in the accumulation of tetracycline by resistant cells appears to be an important element in the mechanism of resistance (11,12,30), but the role of other factors, such as the appearance ofa new protein in resistant cells, has still to be elucidated (2,5,20). Minocycline (7-dimethylamino-6-deoxy-6-demethyltetracycline) is a semisynthetic derivative of tetracycline to which most tetracyclineresistant strains of S. aureus are susceptible (10, 16). Experiments of Kuck and Forbes (17) with E. coli and Sompolinsky and Krausz (33) with S. aureus indicate that tetracycline-resistant cells which retain their susceptibility to minocycline show a decreased accumulation of tetracycline but retain the ability to accumulate minocycline. Resistance to both tetracycline and minocycline determined by some R factors (29, 31) is accompanied by a decrease in the accumulation of both tetracycline and minocycline (17).Phair and Carleton (27) found that S. aureus strains of phage group m, although susceptible ...