The Tet repressor protein (TetR) regulates transcription of a family of tetracycline (tc) resistance determinants in Gram-negative bacteria. The resistance protein TetA, a membrane-spanning H + -[tcÆM]+ antiporter, must be sen-sitively regulated because its expression is harmful in the absence of tc, yet it has to be expressed before the drugs’ concentration reaches cytoplasmic levels inhibitory for protein synthesis.