The in-vitro activity of the novel ketolide HMR 3647 was compared with four other macrolides against 335 strains of staphylococci, pneumococci and enterococci with predetermined susceptibility status to erythromycin. HMR 3647 was the most active agent against staphylococci (irrespective of methicillin resistance) of sensitive (MIC90 = 0.25 mg/L) or inducibly resistant phenotype (MIC90 = 2 mg/L), but was inactive against constitutively resistant strains. HMR 3647 was very active against erythromycin-sensitive enterococci (MIC90 = 0.06 mg/L), irrespective of vancomycin resistance, but less active against strains that were resistant to erythromycin (MIC90 = 32 mg/L). The ketolide was highly active against pneumococci (irrespective of penicillin resistance), both erythromycin sensitive (MIC90 = 0.03 mg/L) and erythromycin resistant (MIC90 = 0.25 mg/L). A bactericidal action was found against some erythromycin-sensitive staphylococci, pneumococci and Enterococcus faecium. The microbiological properties of HMR 3647 are thus superior to those of other macrolides.