Avoparcin is a glycopeptide antimicrobial that is widely used as a growth promoter in animal feeds in portions of Western Europe. Recently, concern has emerged about the possible contribution of avoparcin use to the emergence of glycopeptide resistance in enterococci. Relatively little information exists on the spectrum of activity and potency of avoparcin. We studied the activity of avoparcin compared to vancomycin, teicoplanin, and 3 other antimicrobials against 814 recent human clinical isolates, including Staphylococcus spp. (240 strains), Streptococcus spp. (90 strains), and Enterococcus spp. (60 strains), using reference susceptibility test methods. Our results indicate that avoparcin was less potent than either vancomycin or teichoplanin against staphylococci (MIC50, 4 micrograms/ mL). There was a good correlation of avoparcin MICs with the MICs for vancomycin and teichoplanin for most species; however, the avoparcin MICs for Enterococcus spp. of the vanB phenotype were quite variable (MIC range, 2 to > 16 micrograms/mL). For Staphylococcus haemolyticus, high avoparcin MICs (> or = 16 micrograms/mL) were associated with oxacillin resistance. These results are relevant to the debate concerning the appropriateness of continued use of avoparcin as a growth promoter in animal husbandry. In particular, avoparcin as a glycopeptide with limited potency against some staphylococci seems to represent a theoretically greater risk for selecting glycopeptide resistance among staphylococci, but may not represent any greater threat for the selection of resistance in enterococci.