Replication of lambda plasmid DNA is inhibited in amino acid-starved wild type Escherichia coli cells (i.e., during the stringent response), whereas it proceeds for several hours in relA mutants (i.e., during the relaxed response). It was demonstrated previously that ppGpp-mediated inhibition of transcription starting from the pR promoter is responsible for inhibition of lambda plasmid replication; RNA polymerase function is indispensable for replication of lambda plasmid DNA during the relaxed response. The replication is carried out by the heritable replication complex containing the lambda O protein which is protected from proteases by other elements of this complex. Here we demonstrate that the replication is dependent on DnaG (primase) function. Thus, in amino acid-starved cells, lambda plasmid replication requires RNA polymerase function only for transcriptional activation of ori lambda. We also present evidences that the replication is dependent on the function of DNA gyrase. On the basis of these findings and other recent reports, we demonstrate a model of the regulation of lambda plasmid replication driven by the inherited replication complex. It seems that transcriptional activation of ori lambda indirectly triggers the initiation of lambda plasmid DNA replication at least during the relaxed response.