Streptococcus pneumoniae is the leading cause of community-acquired pneumonia, meningitis, and otitis media in the United States. Because of the emergence of antimicrobial resistance in pneumococci, fluoroquinolones are now recommended by some groups for the treatment of pneumonia in adults, especially when antimicrobial resistance is suspected. Older fluoroquinolones with some antimicrobial activity against the pneumococcus include ciprofloxacin and ofloxacin. Newer fluoroquinolones with higher in vitro activity against the pneumococcus, including levofloxacin, grepafloxacin, gatifloxacin, and moxifloxacin, are available in the United States. Fluoroquinolone resistance to the pneumococcus is rare but may be increasing in Canada. To determine trends of pneumococcal resistance to fluoroquinolones in the United States, invasive pneumococcal disease surveillance data were analyzed from Active Bacterial Core Surveillance (ABCs) during 1995-1999. Fluoroquinolone prescription data were obtained from the National Hospital Ambulatory Medical Care Survey (NHAMCS) during 1993-1998. This report summarizes the results of that analysis, which indicate that pneumococci with reduced susceptibility to fluoroquinolones are appearing in the United States. Appropriate use of antibiotics and continuous prospective surveillance for antimicrobial resistance are necessary to slow the emergence of fluoroquinolone-resistant pneumococci.