The mga regulon of Streptococcus pyogenes contains genes which contribute to the pathogenicity and virulence of this significant human pathogen. Transposon insertional inactivation of the regulatory mga gene in a S. pyogenes strain of the clinically important M1 serotype, blocked the expression of four genes located downstream of mga. These genes encode the M1 protein, the IgG-binding protein H, protein SIC which is an extracellular inhibitor of complement, and the C5a peptidase which interferes with granulocyte migration. The wild-type strain is resistant to phagocytosis and adheres to human skin tissue sections; properties that were lost in the transposon mutant. Moreover, the mutant was less virulent to mice but more cytolytic to human lymphocytes, the latter due to an increased activity of streptolysin S, whereas the production of streptolysin O, another toxin of S. pyogenes, was not affected. The mga mutation was complemented in trans with an intact mga gene which restored the phenotype of the wild-type strain.