The antibiotic peptide nisin produced by Lactococcus lactis is used as a food preservative due to its activity against spores and vegetative cells of Gram-positive bacteria. The post-translational maturation of this secreted peptide includes dehydration of serine and threonine residues, lanthionine formation and a proteolytic processing of 23 amino acids from the N-terminus. Mutations in the nisZ, nisB and nisP genes of the biosynthetic nisZBTCIPRK nisin operon were made by gene replacement or integration of a plasmid. The mutations caused a drastic decrease of the transcription from the promoters upstream of the nisZBTCIPRK and nisFEG operons resulting in loss of nisin production and nisin immunity. The transcription of the nisin operons and nisin immunity could be partially restored by adding nisin to the growth medium of the cells. Nisin induction of the mutant strains also increased the level of the putative immunity NisI protein. These results showed that the nisZBTCIPRK operon is positively autoregulated and that the nisFEG operon is in the same regulon.