Helvecardins (HVCs) A and B were strongly active against aerobic and anaerobic Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), but they were inactive against Gram-negative bacteria and fungi. Though HVC A showed only slightly stronger antimicrobial activity than β-avoparcin (AVP), its in vivo protective activity against S. aureus infection in mice was greatly superior to AVP.