We recently cloned the hyaluronan synthase gene (hasA) from Streptococcus pyogenes (DeAngelis et al., J. Biol. Chem. 268, 19181, 1993). Since this is the first glycosaminoglycan synthase gene to be cloned and these enzymes have also not been purified, nothing is yet known at the molecular level about the similarity or relatedness of hyaluronan synthase to other gene products. We found several proteins in the sequence database with substantial similarities to hyaluronan synthase (HasA), including NodC from Rhizobium, DG42 from Xenopus, and the three chitin synthases (Chs) from Saccharomyces. Like HasA, NodC and the Chs proteins all have at least an N-acetylglucosaminyl transferase activity in common and are membrane-associated. The polymerase chain reaction was also used to show that HasA, and probably the two gene operon for hyaluronan biosynthesis (hasA/hasB), is highly conserved among Group A streptococcal strains. In nine strains, isolated from 1917 through 1993, only five silent mutations were detected. The results show that hyaluronan synthase is highly conserved within Group A strains, although another virulence factor, the M protein, varies considerably in these same strains.