Because of its prominence as a cause of disease in humans, Streptococcus pneumoniae has been the subject of intensive investigation at both the clinical level and the basic scientific level during the past century. In a number of instances, these studies have resulted in important progress toward the comprehension of basic biological principles. The areas advanced by studies of the pneumococcus include an understanding of the concept of pathogenesis of infectious disease; the development of Gram's stain for identification of bacteria in specimens from patients; the elucidation of the role of the bacterial capsule in resistance to phagocytosis by cells of the host's immune system; the demonstration that molecules other than proteins are capable of eliciting the host's humoral immune responses and later, by extension, that isolated bacterial exopolysaccharides can be used safely and effectively as vaccines in humans; the documentation of the efficacy of penicillin; the collection of conclusive evidence that DNA encodes genetic information; and the investigation of putative proteinaceous virulence factors.