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The basis of tetracycline resistance mediated by TetA determinants and joint resistance to tetracycline and minocycline coded by TetB determinants was investigated. The TetA class of determinants was represented by those carried on plasmids pSC101, RPl and pIP7 and TetB by TnlO. The relationships between expression of tetracycline and minocycline resistance and accumulation of these antibiotics suggest that there are three mechanisms of plasmid-determined resistance conferring (1) about a 10-to 20-fold increase in resistance to tetracycline that is not associated with decreased antibiotic accumulation, (2) a 4-to ?' -fold increase in resistance to tetracycline that is associated with decreased drug accumulation, and (3) about a 2-to 3-fold increase in resistance to both tetracycline and minocycline that is not associated with decreased accumulation of either antibiotic. Mechanism 1 was coded by the tetracycline resistance determinant of pSClOl (TetA), mechanisms 1 and 2 by the determinants in RP1 and pIP7 (TetA) and all three mechanisms by TnlO (TetB).