The susceptibilities of clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and enterococci obtained over a 13-year period were tested for trovafloxacin, a new fluoroquinolone, and ciprofloxacin. For MRSA, MIC50 values for trovafloxacin increased from 0.03 microgram/ml to 1 microgram/ml from 1984-1985 to 1995-1996, but were lower than those noted for ciprofloxacin, which increased from 0.25 microgram/ml to > 8 micrograms/ml during the same period. Trovafloxacin also showed lower MIC50 values (0.12-0.25 microgram/ml) than ciprofloxacin (MIC50 of 0.5-1 microgram/ml) for E. faecalis isolates from 1985 through 1991, but against E. faecium and E. faecalis isolated in 1995-1996, the MIC50 values for both trovafloxacin and ciprofloxacin were 2 micrograms/ml and the MIC90 values were > or 8 micrograms/ml. Thus, cross-resistance between fluoroquinolones was shown for both enterococci and MRSA. Whether the greater intrinsic activity of trovafloxacin might allow its use in treating MRSA and enterococcal infections remains to be seen.