In many countries of the developing world, pneumonia remains a leading cause of morbidity and premature mortality. In their quest for effective control measures not dependent on the socioeconomic changes in Western societies that have paralleled a reduction in mortality from pneumonia, these poorer countries are looking towards modern antibiotic therapy and pneumococcal vaccines as short-term approaches to the problem. This paper summarizes information about the response of human populations to Streptococcus pneumoniae with particular reference to the authors' experience in Papua New Guinea, where penicillin resistance is an increasing problem and where pneumococcal vaccines have been shown in field trials to reduce mortality from respiratory disease among both adults and children. In each developing country, basic epidemiologic data are needed to assist in choosing the best available combination of strategies for control of disease due to S. pneumoniae. Our current understanding of the determinants of pneumococcal carriage and pneumococcal disease is still inadequate, however, and there is need for studies of the interaction of the pneumococcus and its host at the mucosal surface to better understand the differences in the behavior observed for the various serotypes.