The suboptimal efficacy of the currently available 23-valent pneumococcal vaccine in the growing population of adults ú65 years old may be related to the limited immunogenicity of the vaccine polysaccharides in this group. In this study, the majority of elderly outpatients with stable chronic illnesses generated a vigorous IgG response to seven vaccine serotypes comparable to that of healthy young adults at 1, 3, and 16 months after immunization. Moreover, the quality and function of anticapsular antibodies, measured as avidity and in vitro opsonization, were comparable between elderly and young subjects over time. However, a subset (Ç20%) of elderly outpatients responded to fewer than two of seven serotypes tested 1 and 3 months after immunization, whereas none of the healthy young adults were such poor responders. Thus, despite the adequate mean immune responses of the elderly as a group, a substantial proportion of elderly persons may have poor responses to the currently available pneumococcal vaccine.Effective prevention of Streptococcus pneumoniae infection control studies. These studies have indicated variable and incomplete protection (60% -81%) from lethal disease among has renewed priority in an era in which the emergence of antibiotic-resistant strains has further compromised efforts to immunized elderly adults [6 -11].The variable efficacy of the pneumococcal vaccine in the reduce early mortality from invasive pneumococcal infection [1 -3]. Although the 23-valent pneumococcal polysaccharide elderly presumably reflects the poor immunogenicity of polysaccharide-based vaccines in this population. Measurements of (PPS) vaccine was formulated to prevent invasive infection in the elderly and other high-risk populations, the protective effi-PPS-specific serum antibodies after pneumococcal immunization of the elderly have produced conflicting results, possibly cacy of this vaccine for the growing population of adults ú65 years old remains uncertain. Doubts regarding the vaccine's because of differences in the selection of subjects (e.g., chronically ill or unusually healthy elderly) or controls (e.g., historical ability to prevent pneumococcal infection in this group were first raised by prospective randomized trials that did not detect controls or cohort) and in methods for assaying antibody concentrations [12 -20]. More importantly, measures of the quality significant reductions in the incidence of pneumococcal bronchitis, pneumonia, or bacteremia in immunized elderly adults of immune responses to pneumococcal vaccine in the elderly have been assayed in only a single report [19], and the func- [4,5]. However, these studies may have lacked sufficient statistical power to exclude the possibility of vaccine efficacy, due tional response to pneumococcal immunization has not been previously assessed. to the unexpectedly low frequency of pneumococcal infection during these trials. Because further clinical trials were not feasiTherefore, in order to establish the effectiveness of pneumococcal vaccination in elderl...