Sorangicin A, a macrolide polyether antibiotic and the ansamycin antibiotic rifampicin inhibit DNA-dependent RNA polymerase to a similar extent. Resistance to sorangicin A is due to a mutation in the RNA polymerase which renders the enzyme less sensitive. Parallel investigations with rifampicin revealed partial cross-resistance, which was more marked in sorangicin A-resistant mutants than in rifampicin-resistant mutants.