Combinatorial peptide display on phage M13 protein pIII was used to discover peptide sequences that selectively bind to ErmC' methyltransferase from Bacillus subtilis. One peptide, Ac-LSGVIAT-NH(2), inhibited methylation in vitro with a 50% inhibitory concentration of 20 microM. Interestingly, the set of six peptides which inhibited ErmC' stimulated ErmSF, a homologous methyltransferase from Streptomyces fradiae. Thus, Ac-LSGVIAT-NH(2) may not act directly at the catalytic center of ErmC', but may modulate its activity by binding at a structurally unrelated, but functionally linked, site.