We observed 42 cases of invasive Streptococcus pneumoniae infections from 1991 through 1993 in southern Taiwan. The antimicrobial susceptibilities and distribution of serotypes of the 42 isolates from these invasive infections were determined. Serotypes 14, 3, 6, 23, 15 and 4 were most commonly identified. Serotypes 14 and 6 most frequently caused infections in pediatric patients, while serotypes 3, 14 and 23 were commonly encountered in adults. Overall, 85.7% of the isolates were included in the serotypes represented in the 23-valent pneumococcal vaccine. Three isolates were intermediately resistant to penicillin and none were fully resistant. Resistance rates were: erythromycin, 61.9%; clindamycin, 47.6%; chloramphenicol, 19%; and tetracycline, 73.8%. Resistance to three or more classes of antibiotics was found in 33.3% of the isolates, in which the majority were serotypes 14 and 6 and nontypeable isolates. Bacteremic pneumonia and primary bacteremia accounted for 64.3% of the infections. Mortality was 42.6%. Factors associated with higher mortality included age of > 16 years, the presence of underlying diseases, development of one or more septic complications, bacteremic pneumonia and the presence of serotype 3 isolates. Rapidly fatal outcome (the illness developed less than 48 hours prior to admission and the death occurred within 48 hours of hospitalization) occurred in 12 (66.7%) of the 18 patients who died. All these patients received adequate antibiotic treatment and aggressive intensive care, indicating the fulminant nature of this infection. Mucoid serotype 3 isolates caused rapidly fatal outcomes. Given the severity of these infections despite adequate antibiotic therapy and the vulnerability of patients with altered immune responses, there is a dire need for introduction of new therapeutic options and preventive measures to prevent mortality due to invasive S. pneumoniae infections.