The ability of the pathogenic Gram-positive bacterium Streptococcus pyogenes (group A streptococcus) to bind fibronectin and adhere to respiratory epithelial cells is dependent on a surface protein called protein F. In this study, we have examined the regulation of expression of protein F and have shown that it is environmentally regulated in response to alterations in atmosphere. In six recent clinical isolates expression of protein F was repressed during growth under reduced concentrations of O2. Expression in an anaerobic environment was induced by both superoxide-generating and redox-altering reagents. However, regulation did not involve mry, a gene that controls expression of several streptococcal surface proteins. Protein F was constitutively expressed in one of two laboratory-passaged strains analysed, and in a complementation analysis using an allele of the gene that encodes protein F (prtF) cloned from a regulated strain and expressed in a constitutive strain, the constitutive phenotype was shown to be dominant in trans. Regulation, as monitored by fusion of prtF to a promoterless chloramphenicol acetyltransferase gene, involved transcriptional control. Environmentally induced alterations in protein F expression affected the ability of the bacterium to adhere to epithelial cells, which suggests that the ability to regulate expression of protein F may be important during infection.