Antibody to the non-serotype-specific cell wall polysaccharide (CWPS) of Streptococcus pneumoniae has been said to confer a degree of non-serotype-specific protection against pneumococcal infection. The hypothesis underlying the present study was that if this antibody is protective, relatively higher levels are likely to be detected in patients who are colonized by pneumococci but do not have infection, those who have febrile bronchitis but do not have pneumonia, and those who have pneumococcal pneumonia but are not bacteremic. Mean IgG reactive with CWPS by ELISA in 15 healthy young adults was 43.9 micrograms/ml and in 126 randomly selected hospital patients of all ages was 41.9 micrograms/ml. In subjects with chronic bronchitis with or without known pneumococcal carriage, mean anti-CWPS IgG was 87.7 micrograms/ml. In three groups of patients (3 with acute purulent tracheobronchitis, 13 with nonbacteremic pneumococcal pneumonia, and 14 with S. pneumoniae bacteremia) at the time of admission, mean antibody levels were essentially identical, 104.9-110.1 micrograms/ml. The data suggest that naturally present anti-CWPS IgG does not protect against the evolution of acute pneumococcal infection from colonization to acute purulent bronchitis, from bronchitis to pneumonia, or from pneumonia to bacteremia.