We measured the in vitro activity of mersacidin (formerly M87-1551) against 183 clinical isolates (vancomycin susceptible) and 12 additional vancomycin-resistant strains of Gram-positive bacteria. The activity for mersacidin increased an average twofold (range, 1.7- to 7.6-fold) in a calcium-enriched medium. The minimum inhibitory concentration (MIC)90 for mersacidin was 8-32 times higher than vancomycin for staphylococci, 4-64 times higher for enterococci, and up to 32 times higher for other organisms tested. The MIC90 for MDL 62873, a comparison compound, was less-than-or-equal-to 0.5-mu-g/ml for all species except Staphylococcus haemolyticus (MIC90, 4-mu-g/ml), and it was greater-than-or-equal-to 4-fold more active than vancomycin. Against selected vancomycin-resistant strains, mersacidin had MICs greater-than-or-equal-to 16-mu-g/ml for enterococci, 4-32-mu-g/ml for Pediococcus, and less-than-or-equal-to 2-mu-g/ml for Leuconostoc species. Mersacidin may have some clinical utility in documented infections caused by staphylococci, nonenteric streptococci, Pediococcus, and Leuconostoc.