As the most commonly used fluoroquinolone in the United States since 1987, ciprofloxacin has exerted the greatest selective pressure on S. pneumoniae and provides a valuable marker to evaluate the actual and potential emergence of fluoroquinolone resistance in this species. Analysis of susceptibility results obtained with 5,640 strains collected from throughout the United States showed that only 16 (0.3%) of the isolates demonstrated MICs of > or =4 microg/ml. The prevalence of this phenotype was significantly higher (P < 0.05) among penicillin-resistant populations, among isolates from patients >64 years old, and among respiratory isolates. However, >99% of strains had MICs of <4 microg/ml regardless of the risk group examined, and the MIC population distributions were the same for each risk group. These findings demonstrate that the phenotype of a MIC of > or =4 microg/ml remains uncommon after 10 years of ciprofloxacin use; however, these findings are no reason to become complacent with regard to appropriate use of fluoroquinolones and the need to carefully track resistance trends. Equally important is careful analysis of data that result from surveillance in terms of risk factors and other associated trends so that resistance and susceptibility, and their consequences, are neither over- nor underestimated.