The in vitro activity of levofloxacin against 506 Gram-positive bacteria was compared with those of D(-)ofloxacin, ofloxacin, ciprofloxacin, and sparfloxacin. Levofloxacin was generally twice as active as ofloxacin against these organisms (range, 0-3 twofold dilutions). Sparfloxacin appeared to have the greatest activity overall, but for several groups of organisms minimum inhibitory concentrations (MIC(90)s) of this compound were within one twofold dilution of those of levofloxacin. Resistance to levofloxacin (MIC greater than or equal to 8 mu g/ml) was not encountered among streptococcal species, was rare in methicillin-susceptible staphylococci (1.7%), and was infrequent in vancomycin-susceptible Enterococcus faecalis and Enterococcus faecium (8.7%). Resistance tons more common among vancomycin-resistant enterococci and methicillin-resistant staphylococci.