The comparative in vitro activity of HMR 3004 and HMR 3647, new ketolide antibiotics, was tested by a standard agar dilution technique against 221 pneumococcal strains, including isolates with intermediate levels of resistance to penicillin and erythromycin-resistant isolates. The ketolides were more active than other macrolides and showed excellent activity against erythromycin-resistant strains. All the strains were inhibited by < or = 2 micrograms of HMR 3004/ml or by < or = 0.5 microgram of HMR 3647/ml.