The antibacterial activity of SCH 27899, was compared with vancomycin in vitro against 210 recent clinical isolates representing eight major genera of Gram-positive organisms. MIC90 values for everninomicin were consistently better than those of vancomycin for all Gram-positive bacteria tested. Although everninomicin was less bactericidal than vancomycin against staphylococci, it was inhibitory against vancomycin-resistant enterococci. This novel antibiotic may, therefore, provide a clinical alternative to penicillin and vancomycin for therapy of Gram-positive infections.