The γ-butyrolactone regulatory system triggers secondary metabolism and/or morphological development in the Gram-positive, soil-dwelling, filamentous bacterial genus Streptomyces. The representative of the γ-butyrolactones is A-factor in Streptomyces griseus. AfsA is an enzyme for A-factor biosynthesis and ArpA is the A-factor receptor protein that serves as a transcriptional factor by using A-factor as the ligand. Analysis of evolutional relations between AfsA including its homologues and ArpA including its homologues, all of which are widely distributed in Streptomyces, revealed great differences in the topologies of their phylogenetic trees. Therefore, the combinations of AfsA homologues and ArpA homologues in a given Streptomyces strain appear to have changed during the evolution. Even if an afsA homologue and an arpA homologue locate adjacently on the chromosome, the evolutional history of the individuals was found to be different in some Streptomyces strains. In addition, the phylogenetic analyses suggested that the ancestral ArpA protein had existed and functioned as a DNA-binding protein, not as a γ-butyrolactone receptor, before the appearance of a γ-butyrolactone receptor protein in the course of the bacterial evolution. Some Streptomyces strains have plasmids encoding AfsA/ArpA homologues, which suggests that plasmids have played an important role in the distribution of afsA/arpA homologues. During the evolution, once a Streptomyces strain acquired different afsA/arpA homologues, it may have developed a new γ-butyrolactone regulatory system reconstructing the regulatory systems for secondary metabolism and/or morphogenesis. This idea is consistent with the diverged combination of AfsA homologues and ArpA homologues in a Streptomyces strain.