Intrinsic antimicrobial resistance of Escherichia coli is elicited by the gàne products of the multi-drug ef flux acrAB-tolC operon. The primary regulation of acrAB has been investigated in these studies and it has been established by chemostat culture that the expression of acrAB was inversely related to growth rate, and this was irrespective of the limiting nutrient. This regulation was not OS_dependent as the expression of acrAB increases during stationary phase in the batch culture of an rpoS mutant. In the same rpoS mutant it was found that there was an even greater derepression of acrR transcription. When rpoD was overexpressed from an inducible multicopy plasmid, it was determined that the repression by o was not through competition with a 70 for the ENA-polymerase core. It has also been demonstrated that the transcription of acrAB was more readily inhibited by AcrR than the transcription of acrR. The role of ppGpp in the regulation of acrAB or acrR expression was not established in these studies, however, evidence was presented for positive regulation by cyclic AMP, and the possible role of negative supercoiling was discussed.