Between August 1996 and July 1997, 550 clinically significant Streptococcus pneumoniae isolates were collected from 14 geographically separate laboratories in Taiwan. These isolates were serotyped and MICs were determined by agar dilution. Among serotypes covered by the 23-valent vaccine, types 19F, 19A, 23F, 23A and 6B dominated, comprising 255 isolates; among non-vaccine serotypes, types 35, 39, 34, 13 and 31 dominated, comprising 118 isolates. Of the 550 isolates, 310 (56.4%) were resistant to penicillin G (MIC 0. 12 mg/L), 238 (43.3%) with intermediate resistance (MIC 0.12-1 mg/L) and 72 (13.1%) with high-level resistance (MIC 2 mg/L). Most non-susceptible pneumococci were of serotypes 19F and 23F; non-susceptible isolates of these serotypes were distributed across all of Taiwan. Fourteen other antibiotics were tested; 83% of the isolates were resistant to tetracycline, 78% to azithromycin, 74% to erythromycin, 54% to clindamycin and 23% to chloramphenicol. Thus, macrolides can no longer be used as first line agents to treat pneumococcal infections in Taiwan. Multi-resistance (isolates resistant to three or more chemically unrelated antibiotics) was found in each serotype or group, but mostly in types 19F and 23F. The emergence of such strains complicates antibiotic selection, but both types are covered by the 23-valent vaccine, as were 82% of the isolates from blood and eight of the nine from cerebrospinal fluid. Good antibiotic control and appropriate use of this vaccine may improve the current problem in Taiwan, especially for the elderly.