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We determined the susceptibilities of 265 invasive isolates of pneumococci obtained during 1995 to 2001 in Hong Kong to 11 antimicrobial agents and their serotypes. Overall, 62.6% isolates were susceptible to penicillin, 20% were intermediately resistant, and 17.4% were resistant. The overall prevalence of levofloxacin resistance (MIC >8 μg/mL) was 3.8% but increased to 15.2% among the penicillin-resistant isolates. All levofloxacin-resistant isolates were clonally related; had reduced susceptibility to penicillin, cefotaxime, and clarithromycin; and were derived from adults >50 years of age. Of the penicillin-nonsusceptible pneumococci, 90% were from children <5 years of age, and 54.8% from persons of all ages are of serotypes that are included in the 7-valent pneumococcal conjugate vaccine; 93.5% from children <5 years of age and 93% from persons of all ages are of serotypes that are included in the 23-valent polysaccharide vaccine.