The in vitro activity of trovafloxacin (CP-99,219), a new fluoroquinolone, was compared with the in vitro activities of other commonly used quinolones and other antimicrobial agents against 445 gram-positive microorganisms isolated between 1986 and 1995 from patients with endocarditis and those with other bloodstream infections. The MICs at which 90% of the isolates are inhibited (MIC 90 ) of trovafloxacin for methicillinsusceptible staphylococci, viridans group streptococci, and enterococci were 0.06, 0.25, and 0.5 mg/liter, respectively. The MIC 90 of trovafloxacin for vancomycin-resistant enterococci as well as for methicillinresistant Staphylococcus aureus and methicillin-susceptible and ciprofloxacin-resistant S. aureus, isolated from sources other than blood, was 1 mg/liter. For the quinolones the rank order of activity was trovafloxacin > sparfloxacin > ciprofloxacin ؍ ofloxacin > pefloxacin. Depending on the species tested, trovafloxacin was 4to 64-fold more active than ciprofloxacin. Further experimental and in vivo studies are warranted to evaluate the efficacy of trovafloxacin in the treatment of bacterial endocarditis and other infections caused by grampositive organisms.