The antimicrobial susceptibilities and serotypes of 115 Streptococcus pneumonia strains isolated in southern Taiwan from January 1990 to December 1993 were determined. All isolates were susceptible to cephalothin, cefotaxime, trimethoprim/sulfamethoxazole and vancomycin, and 14 of the isolates were resistant to penicillin G. The oxacillin disk method for presumptive detection of resistance to penicillin had a sensitivity of 85.7% and specificity of 97.0%. Resistance rates were as follows: erythromycin 62.2%, tetracycline 71.3%, clindamycin 46.1% and chloramphenicol 19.1%. Eighty-four percent of the isolates were resistant to one or more of the antibiotic tested. Multiple resistance (to three or more classes of antibiotics) was identified in 40.9% of all the isolates and 100% of penicillin-resistant isolates. The predominant serotypes were: 14 (19.1%), 3 (17.4%), 23 (15.7%), 6 (10.4%), and 15 (6.1%). Serotypes 14 and 63 most commonly caused childhood infections, while serotypes 3 and 23 were frequently encountered in adults. The proportion of coverage in 23-valent pneumococcal polysaccharide vaccine was 92.2%, if vaccine-related serotypes were considered to be cross-protecting. Seven (58%) of 12 typable penicillin-resistant isolates belonged to serotype 23 and two (16.7%) to serotype 6. All isolates of serotype 14, 23, 15 and 19 were resistant to one or more antibiotics. Multiple drug resistance was frequently associated with serotype 23 (31.9%), 14 (23.4%) and 6 (17.0%). Sixty-five percent of isolates of serotype 3 were susceptible to all antibiotics tested. The high level of antimicrobial resistance in S. pneumoniae mandates the continuous surveillance of resistance and the strict control of antibiotic use in Taiwan.