There is a high prevalence of beta-lactam- and macrolide-resistant Streptococcus pneumoniae in Taiwan. To understand the in vitro susceptibilities of recent isolates of S. pneumoniae to fluoroquinolones and telithromycin (which is not available in Taiwan), the MICs of 23 antimicrobial agents for 936 clinical isolates of S. pneumoniae isolated from different parts of Taiwan from 2000 to 2001 were determined by the agar dilution method. Overall, 72% of isolates were not susceptible to penicillin (with 61% being intermediate and 11% being resistant) and 92% were resistant to erythromycin. Telithromycin MICs were >or=1 microg/ml for 16% of the isolates, and for 99% of these isolates the MICs of all macrolides tested were >or=256 microg/ml; all of these isolates had the constitutive macrolide-lincosamide-streptogramin B phenotype. Eighty-eight percent of the isolates were resistant to three or more classes of drugs. The ciprofloxacin MICs were >or=4 microg/ml for six (0.6%) isolates from five patients collected in 2000 and 2001, and the levofloxacin MICs were >or=8 microg/ml for five of these isolates. Seven isolates for which ciprofloxacin MICs were >or=4 microg/ml, including one isolate recovered in 1999, belonged to three serotypes (serotype 19F, five isolates; serotype 23A, one isolate; and serotype 23B, one isolate). The isolates from the six patients for which ciprofloxacin MICs were >or=4 microg/ml had different pulsed-field gel electrophoresis profiles and random amplified polymorphic DNA patterns, indicating that no clonal dissemination occurred over this time period. Despite the increased rate of fluoroquinolone use, the proportion of pneumococcal isolates for which ciprofloxacin MICs were elevated (>or=4 microg/ml) remained low. However, the occurrence of telithromycin resistance is impressive and raises concerns for the future.