A new series of erythromycin A derivatives, the 6-O-heteroarylcarbamoyl-11,12-lactoketolides, with activity against macrolide-resistant streptococci, are described. Structurally, these macrolide antibiotics are characterized by a heteroaryl side chain attached to the macrolactone core through a carbamate linkage at the C6 position, as well as 11,12-gamma-lactone and 3-keto functionalities. The synthesis and antibacterial activity of this new series of ketolides are discussed.