BACKGROUND: The control of antibiotic production in Streptomyces coelicolor A3(2) involves complicated regulatory networks with multiple regulators controlling the expression of antibiotic biosynthetic pathways. One such regulatory network is that of the γ-butyrolactones, the so-called S. coelicolor butanolide (SCB) system. The γ-butyrolactones in this system serve as signalling molecules and bind to the receptor protein ScbR, releasing the repression of its target genes. The resulting expression changes affect the production of the two pigmented antibiotics Act and Red, as well as the transcription of the cpk antibiotic biosynthesis gene cluster and the synthesis of the γ-butyrolactones themselves. RESULTS: We identified a natural variant of ScbR in S. coelicolor (ScbRM600) that differs from ScbR in the genome-sequenced strain M145 (ScbRM145) by a single amino acid change, R120S. ScbRM600 is impaired in its DNA binding ability and alters the expression of the pathway-specific regulatory genes of the red and cpk antibiotic biosynthesis gene clusters. Also, expression of the γ-butyrolactone biosynthesis gene scbA and production of the signalling molecules is slightly reduced. CONCLUSIONS: The γ-butyrolactone receptor, ScbR, plays a key role in the SCB regulatory cascade and in determining the onset of the expression of the antibiotic regulatory genes.