Fractions from a partition of a total extract of Hypericum ascyron. L. and Hypericum japonicum. Thunb. ex Murray were investigated for their antibacterial activity against a strain of multidrug-resistant (MDR) Staphylococcus aureus. possessing the NorA multidrug-efflux transporter, the major characterized MDR pump in this species. The hexane fraction of Hypericum ascyron. and the n.-BuOH fraction of H. japonicum. both showed appreciable antibacterial activities with minimum inhibitory concentration (MIC) values of 128 µg/ml for both fractions. Given the complexity of these extracts and the relevance of the NorA efflux mechanism in clinical isolates of Staphylococcus aureus., these results highlight the potential of the genus Hypericum. as a source of new antibacterial drug-leads.