Ketolides belong to a new class of semi-synthetic 14-membered-ring macrolides, which differ from erythromycin A by having a 3-keto group instead of the neutral sugar L-cladinose. The ability of these molecules and their L-cladinose counterparts to induce MLS(B) resistance in staphylococci (one strain) and streptococci (two strains) was investigated using a disc agar susceptibility method as well as measuring induction kinetics. All 14- and 15-membered ring macrolides tested showed inducing activity. In contrast, ketolides were clearly unable to induce MLS(B) resistance, a result consistent with the high in-vitro activity of this new class of antibiotics against erythromycin A-inducible resistant bacteria.