The susceptibilities of clinical isolates to fluoroquinolones (FQs) and other antimicrobial agents were surveyed to obtain an accurate understanding of the trends in incidence and antimicrobial resistance. The samples were collected from across Japan, biennially, between 1994 and 2002 and a defined level of resistance to FQ determined. Streptococcus pneumoniae and Haemophilus influenzae exhibited stable and high rates of susceptibility to FQ over the period examined. For methicillin-resistant Staphylococcus aureus the rate of resistance to FQ was 80%-90%, markedly higher than that of methicillin-susceptible S. aureus. The rate of FQ-resistant Escherichia coli increased rapidly to approximately 10% for samples after 2000. Of 696 E. coli isolates collected in 2002, 13 produced an extended-spectrum beta-lactamase (ESBL), with 6 of 13 ESBL-producing isolates being FQ-resistant. No FQ resistance in clinical isolates of Salmonella spp. was detected in any of the surveys. The rate of FQ resistance to Pseudomonas aeruginosa isolated from urinary tract and respiratory tract infections was 40%-60% and 15%-25%, respectively.