The antimicrobial activity of evernimicin (formerly SCH 27899), a novel oligosaccharide antimicrobial of the everninomicin class, was evaluated against four groups of Gram-positive pathogens: (i) Streptococcus pneumoniae (n = 1452); (ii) methicillin- or oxacillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci (MR-CoNS; n = 1427); (iii) enterococci (n = 1517); and (iv) non-pneumococcal streptococci (n = 1388), using the Etest method at each study centre throughout Eastern and Western Europe, Scandinavia, South Africa, Turkey and North America. Comparative MICs were determined for a variety of reference compounds, including vancomycin, quinupristin/dalfopristin, chloramphenicol, penicillin, ampicillin, oxacillin, ceftriaxone and ciprofloxacin. Evernimicin was highly active against all strains tested, with MIC90 values less than or equal to1.0 mg/L, ranging from 0.047 mg/L against S. pneumoniae to 1.0 mg/L against MRSA/MR-CoNS and enterococci. Compared with the reference agents, the MIC90 of evernimicin were lower against all species. Against MRSA and MR-CoNS the MIC(90)s of evernimicin, quinupristin/dalfopristin and vancomycin (the three most active agents) were 1.0, 1.5 and 3.0 mg/L, respectively. Against all species tested, the relative activities and spectra of these agents were: evernimicin > vancomycin > quinupristin/dalfopristin. The Etest proved to be reliable and reproducible, despite occasional interpretive difficulties caused by observer Inexperience. Quality control results were excellent among the 33 participant sites. The results of this in vitro, multicentre, multinational study demonstrate that evernimicin possesses high antimicrobial activity against Gram-positive organisms that compares favourably with established antibacterial treatments and newer agents such as quinupristin/dalfopristin. Further clinical investigations of everninomicin class compounds appear warranted.