The pneumococci possess, in addition to type-specific capsular polysaccharides, a number of antigens common to the species. Antibodies to phosphocholine (PC), a major determinant of C-carbohydrate, have been shown to protect mice from experimental pneumococcal infection, but little is known of the role of anti-PC antibodies in humans or the extent to which anti-PC levels are affected by carriage or infection. We examined 115 sera from 30 infants, who were followed propsectively from birth through 4 years of age, for the presence of immunoglobulin M antibody to PC, using a solid-phase radioimmunoassay method. Infants were found to develop antibody to PC in response to pneumococcal carriage and infection, and nearly all infants developed some antibody. Antibody levels increased with age. By using a regression model including both age and nasopharyngeal carriage of pneumococci, anti-PC levels were found to be highest after exposure to two or three different types of pneumococci; levels were highest soon after acquisition of pneumococci and declined thereafter.