The in vitro activity of moxifloxacin, formerly BAY 12-8039, against gram-positive bacteria was tested by the agar dilution method. A total of 189 isolates that included Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, streptococci, rhodococci, leuconostocs, pediococci, lactobacilli, and diphtheroids were tested. Moxifloxacin showed greater potency than ciprofloxacin against S. aureus, streptococci, and enterococci, having Minimal Inhibitory Concentrations (MICs) lower than those of ciprofloxacin by 2- to 64-fold. This improved activity was most prominent for S. aureus. Moxifloxacin was active against Leuconostoc and Rhodococcus species. Time-kill studies using moxifloxacin at a concentration of 3 micrograms/mL against one isolate each of methicillin-resistant S. aureus (MSSA) (MIC, 0.031 microgram/mL), MRSA (MIC, 1 microgram/mL), two isolates of E. faecalis (MICs, 0.25 and 2 micrograms/mL), and two isolates of vancomycin-resistant E. faecium (MICs, 0.25 and 2 micrograms/mL) revealed an average decrease in colony forming unit (CFU) by 3.8, 0.4, 4.0, 2.0, 4.2, and 1.8 log10 CFU/mL at 24 h, respectively. Moxifloxacin is a new 8-methoxyquinolone with improved in vitro activity against gram-positive bacteria. Further studies of the in vivo activity of this compound appear warranted.